Benzoheterocyclic compounds

ABSTRACT

Novel benzoheterocyclic compounds of the formula: ##STR1## wherein R 1  is H, halogen, alkyl, optionally substituted amino, alkoxy; R 2  is H, halogen, alkoxy, phenylalkoxy, OH, alkyl, optionally substituted amino, carbamoyl-alkoxy, optionally substituted amino-alkoxy, optionally substituted benzoyloxy; R 3  is a group: --NR 4  R 5  or --CO--NR 11  R 12  ; R 4  is H, optionally substitued benzoyl, alkyl; R 5  is a group: ##STR2## [R 16  is halogen, optionally substituted alkyl, OH, alkoxy, alkanoyloxy, alkylthio, alkanoyl, carboxy, alkoxycarbonyl, CN, NO 2 , optionally substituted amino, phenyl, cycloalkyl, etc., or a group: --O--A--NR 6  R 7  ; m is 0 to 3], phenyl-alkoxycarbonyl, alkanoyl, phenylalkanoyl, etc.; R 11  is H or alkyl; R 12  is cycloalkyl or optionally substituted phenyl; and W is a group: --(CH 2 ) p  (p is 3 to 5) or --CH═CH--(CH 2 ) q  (q is 1 to 3), the carbon atom of these groups beign optionally replaced by O, S, SO, SO 2  or a group: --N(R 13 )-- and further these groups having optionally 1 to 3 substituents of alkyl, alkoxycarbonyl, carboxy, OH, O, alkanoyloxy, etc., which have excellent vasopressin antagonistic activities and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor, and a vasopressin antagonistic composition containing the compound as the active ingredient.

This is a divisional of application Ser. No. 08/474,544 filed Jun. 7,1995 (now U.S. Pat. No. 5,753,677 issued May 19, 1998), which is adivisional of application Ser. No. 08/076,804 filed Jun. 10, 1993 (nowU.S. Pat. No. 5,559,230 issued Sep. 24, 1996), which is a Divisional ofapplication Ser. No. 07/851,541 filed Mar. 13, 1992 (now U.S. Pat. No.5,258,510 issued Nov. 2, 1993), which is a Continuation-In-Part ofapplication Ser. No. 07/762,015 filed Jun. 19, 1991 (now Abandoned)which is a national stage of PCT/JP80/01340, filed Oct. 18, 1990, eachof which is incorporated in its entirety by reference.

TECHNICAL FIELD

This invention relates to novel benzoheterocyclic compounds which haveexcellent vasopressin antagonistic activities and are useful asvasodilator, hypotensive agent, water diuretics, platelet aggregationinhibitor.

DISCLOSURE OF THE INVENTION

The benzoheterocyclic compounds of this invention have the followingformula: ##STR3## wherein R¹ is hydrogen atom, a halogen atom, a loweralkyl, an amino having optionally a lower alkyl substituent, or a loweralkoxy,

R² is hydrogen atom, a halogen atom, a lower alkoxy, aphenyl(lower)alkoxy, hydroxy, a lower alkyl, an amino having optionallya lower alkyl substituent, a carbamoyl-substituted lower alkoxy, anamino-substituted lower alkoxy having optionally a lower alkylsubstituent, or a benzoyloxy which has optionally a halogen substituenton the phenyl ring,

R³ is a group of the formula: ##STR4## or a group of the formula:##STR5## R⁴ is hydrogen atom, a benzoyl which has optionally a halogensubstituent on the phenyl ring, or a lower alkyl,

R⁵ is a group of the formula: ##STR6## [wherein R¹⁶ is a halogen atom; alower alkyl which has optionally a substituent selected from a halogenatom and hydroxy; hydroxy; a lower alkoxy; a lower alkanoyloxy; a loweralkylthio; a lower alkanoyl; carboxy; a lower alkoxycarbonyl; cyano;nitro; an amino which has optionally a substituent selected from a loweralkyl and a lower alkanoyl; phenyl; a cycloalkyl; a loweralkanoyloxy-substituted lower alkoxy; a carboxy-substituted loweralkoxy; a halogen-substituted lower alkoxy; a carbamoyl-substitutedlower alkoxy; a hydroxy-substituted lower alkoxy; a loweralkoxycarbonyl-substituted lower alkoxy; a phthalimido-substituted loweralkoxy; an aminocarbonyl-lower alkoxy having a lower alkyl substituent;or a group of the formula: ##STR7## (A is a lower alkylene, and R⁶ andR⁷ are the same or different and are each hydrogen atom, a lower alkylhaving optionally a hydroxy substituent, a lower alkanoyl, or benzoyl,or R⁶ and R⁷ may bind together with nitrogen atom to which they bond toform a 5- or 6-membered saturated heterocyclic group with or withoutbeing intervened with nitrogen or oxygen atom wherein the heterocyclicgroup has optionally a substituent selected from piperidinyl and a loweralkyl); and m is an integer of 0 to 3], a phenyl-lower alkoxy-carbonyl,a lower alkanoyl, a phenyl-lower alkanoyl, a cycloalkyl-lower alkanoyl,a cycloalkylcarbonyl, tricyclo[3.3.1.1]-decanylcarbonyl,naphthylcarbonyl, pyridylcarbonyl, furoyl, thenoyl, a phenoxy-loweralkanoyl which phenyl ring has optionally 1 to 3 substituents selectedfrom a lower alkyl, a lower alkoxy and an amino having optionally alower alkanoyl substituent, a phthalimido-substituted lower alkanoyl, alower alkoxycarbonyl-lower alkanoyl, a carboxy-lower alkanoyl, anaphthyloxy-lower alkanoyl, a halogen-substituted lower alkanoyl, agroup of the formula: ##STR8## (wherein R⁸ is hydrogen atom, a loweralkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, anamino-lower alkanoyl having optionally a lower alkyl substituent, or alower alkanoyl), an anilinocarbonyl which has optionally a lower alkylsubstituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl whichhas optionally a substituent selected from a halogen atom and a loweralkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula:##STR9## (wherein B is a lower alkylene, n is an integer of 0 or 1, andR⁹ and R¹⁰ are the same or different and are each hydrogen atom, a loweralkyl having optionally a hydroxy substituent, a cycloalkyl, aphenyl-lower alkyl, a lower alkanoyl, a lower alkenyl, a phenoxy-loweralkyl, a phenyl which has optionally 1 to 3 substituents selected froman amino-lower alkyl having optionally a lower alkanoyl substituent, alower alkyl, a lower alkoxy and a halogen atom, aphthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with nitrogen atom to which they bond to form a 5-or 6-membered saturated heterocyclic group with or without beingintervened with nitrogen or oxygen atom wherein the heterocylic grouphas optionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl),

R¹¹ is hydrogen atom or a lower alkyl,

R¹² is a cycloalkyl, or a phenyl which has optionally 1 to 3substituents selected from a lower alkoxy, a lower alkyl and a halogenatom,

W is a group of the formula: --(CH₂)_(p) -- (p is an integer of 3 to 5),or a group of the formula: --CH═CH--(CH₂)_(q) -- (q is an integer of 1to 3), the carbon atom of these groups: --(CH₂)_(p) -- and--CH═CH--(CH₂)_(q) -- being optionally replaced by oxygen atom, sulfuratom, sulfinyl, sulfonyl, or a group of the formula: ##STR10## (R¹³ ishydrogen atom, a cycloalkyl, or a lower alkyl), and further said--(CH₂)_(p) -- and --CH═CH--(CH₂)_(q) -- groups having optionally 1 to 3substituents selected from a lower alkyl having optionally a hydroxysubstituent, a lower alkoxycarbonyl, carboxy, hydroxy, oxo, a loweralkanoyloxy having optionally a halogen substituent, an amino-loweralkyl having optionally a substituent selected from a lower alkyl and alower alkanoyl, a lower alkanoyloxy-substituted lower alkyl, a loweralkyl sulfonyloxy-lower alkyl, an azido-lower alkyl, a group of theformula: ##STR11## an aminocarbonyloxy having optionally a lower alkylsubstituent, a lower alkoxy, a lower alkoxycarbonyl-substituted loweralkoxy, a carboxy-substituted lower alkoxy, an aminocarbonyl-loweralkoxy having optionally a lower alkyl substituent, an amino-loweralkoxy having optionally a substituent selected from a lower alkyl and alower alkanoyl, a phthalimido-substituted lower alkoxy, hydroxyimino, alower alkanoyloxy-imino, a lower alkylidene, a halogen atom, azido,sulfoxyimino, a group of the formula: ##STR12## (R⁸¹ is hydrogen atom ora lower alkyl), hydrazino, pyrrolyl, an amino-lower alkanoyloxy havingoptionally a lower alkyl substituent, a group of the formula: ##STR13##(A is as defined above, and R⁸² and R⁸³ are the same or different andare each hydrogen atom, a lower alkyl, a carbamoyl-substituted loweralkyl, a hydroxy-substituted lower alkyl, or a pyridyl-lower alkyl, orR⁸² and R⁸³ may bind together with nitrogen atom to which they bond toform a 5- or 6-membered saturated heterocyclic group with or withoutbeing intervened with nitrogen, oxygen or sulfur atom wherein theheterocyclic group has optionally a substituent selected from oxo, alower alkyl, a lower alkanoyl, and carbamoyl), and a group of theformula: ##STR14## (wherein n is as defined above, and R¹⁴ and R¹⁵ arethe same or different and are each hydrogen atom, a lower alkyl, a loweralkenyl, a lower alkanoyl, a cycloalkyl, an oxiranyl-substituted loweralkyl, a lower alkyl having optionally 1 to 2 substituents selected froma lower alkoxy, hydroxy and an amino having optionally a lower alkylsubstituent, a phenyl-lower alkyl, a pyridyl-lower alkyl, a loweralkylsulfonyl, benzoyl, a lower alkoxy-carbonyl, anilinocarbonyl, anaminocarbonyl having optionally a lower alkyl substituent, acyano-substituted lower alkyl, a lower alkoxycarbonyl-substituted loweralkyl, a carbamoyl-substituted lower alkyl, a carboxy-substituted loweralkyl, a tetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent on the piperidinyl ring, ahalogen-substituted lower alkanoyl, an imidazolyl-substituted loweralkanoyl, an amino-lower alkanoyl having optionally a substituentselected from a lower alkyl and a lower alkoxycarbonyl, anaminocarbonyl-lower alkyl having optionally a lower alkyl substituent,or a phenyl-lower alkoxycarbonyl, or R¹⁴ and R¹⁵ may bind together withnitrogen atom to which they bond to form a 5- or 6-membered saturatedheterocyclic group with or without being intervened with nitrogen oroxygen, wherein the heterocyclic group may optionally have a substituentselected from a lower alkyl, a phenyl-lower alkyl or a lower alkanoyl).

The benzoheterocyclic compounds of the formula (1) and their salts haveexcellent vasopressin antagonistic activities and vasodilating activity,hypotensive activity, activity for inhibiting saccharide release inliver, activity for inhibiting growth of mesangium cells, water diureticactivity, platelet agglutination inhibitory activity and are useful asvasodilator, hypotensive agent, water diuretics, platelet agglutinationinhibitor and are used for the prophylaxis and treatment ofhypertension, edema, ascites, heart failure, renal function disorder,vasopressin parasecretion syndrome (SIADH), hepatocirrhosis,hyponatremia, hypokaliemia, diabetic, circulation disorder, and thelike.

Each group in the above formula (1) includes specifically the followinggroups.

The "lower alkoxy" includes a straight chain or branched chain alkoxygroup having 1 to 6 carbon atoms, for example, methoxy, ethoxy, propoxy,isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, and the like.

The "lower alkyl" includes a straight chain or branched chain alkylgroup having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl,isopropyl, butyl, tert-butyl, pentyl, hexyl, and the like.

The "halogen atom" includes fluorine atom, chlorine atom, bromine atomand iodine atome.

The "amino having optionally a lower alkyl substituent" includes anamino having optionally one or two substituents selected from a straightchain or branched chain alkyl group having 1 to 6 carbon atoms, forexample, amino, methylamino, ethylamino, propylamino, isopropylamino,butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino,diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino,N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino,N-methyl-N-hexylamino, and the like.

The "lower alkenyl" includes a straight chain or branched chain alkenylgroup having 2 to 6 carbon atoms, for example, vinyl, allyl, 2-butenyl,3-butenyl, 1-methylallyl, 2-pentenyl, 2-hexenyl, and the like.

The "lower alkyl which has optionally a substituent selected from ahalogen atom and hydroxy" includes a straight chain or branched chainalkyl group having 1 to 6 carbon atoms which may optionally have 1 to 3substituents selected from a halogen atom and hydroxy, for example, inaddition to the above-mentioned lower alkyl groups, hydroxymethyl,2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihyroxypropyl,4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl,5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl,2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl,chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl,dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl,2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl,4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl,3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dichlorohexyl, and the like.

The "lower alkylene" includes a straight chain or branched chainalkylene group having 1 to 6 carbon atoms, for example, methylene,ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene,1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene,pentamethylene, hexamethylene, and the like.

The "lower alkanoyloxy" includes a straight chain or branched chainalkanoyloxy group having 1 to 6 carbon atoms, for example, formyloxy,acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy,tert-butylcarbonyloxy, hexanoyloxy, and the like.

The "lower alkylthio" includes a straight chain or branched chainalkylthio group having 1 to 6 carbon atoms, for example, methylthio,ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio,pentylthio, hexylthio, and the like.

The "lower alkanoyl" includes a straight chain or branched chainalkanoyl group having 1 to 6 carbon atoms, for example, formyl, acetyl,propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl,hexanolyl, and the like.

The "lower alkoxycarbonyl" includes a straight chain or branched chainalkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety,for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl,pentyloxycarbonyl, hexyloxycarbonyl, and the like.

The "amino having optionally a substituent selected from a lower alkyland a lower alkanoyl" includes an amino having optionally one or twosubstituents selected from a straight chain or branched chain alkylgroup having 1 to 6 carbon atoms and a straight chain or branched chainalkanoyl group having 1 to 6 carbon atoms, for example, amino,methylamino, ethylamino, propylamino, isopropylamino, butylamino,tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino,dipropylamino, dibutylamino, dipentylamino, dihexylamino,N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino,N-methyl-N-hexylamino, N-methyl-N-acetylamino, N-acetylamino,N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino,N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino,N-ethyl-N-acetylamino, and the like.

The "cycloalkyl" includes a cycloalkyl having 3 to 8 carbon atoms, forexample, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, and the like.

The "lower alkanoyloxy-substituted lower alkoxy" includes a straightchain or branched chain alkoxy group having 1 to 6 carbon atoms which issubstituted by a straight chain or branched chain alkanoyloxy grouphaving 2 to 6 carbon atoms, for example, acetyloxymethoxy,2-propionyloxyethoxy, 1-butyryloxyethoxy, 3-acetyloxypropoxy,4-acetyloxybutoxy, 4-isobutyryloxybutoxy, 5-pentanoyloxypentyloxy,6-acetyloxyhexyloxy, 6-tert-butylcarbonyloxyhexyloxy,1,1-dimethyl-2-hexanoyloxyethoxy, 2-methyl-3-acetyloxypropoxy, and thelike.

The "carbamoyl-substituted lower alkoxy" includes acarbamoyl-substituted alkoxy group wherein the alkoxy moiety is astraight chain or branched chain alkoxy group having 1 to 6 carbonatoms, for example, carbamoylmethoxy, 2-carbamoylethoxy,1-carbamoylethoxy, 3-carbamoylpropoxy, 4-carbamoylbutoxy,5-carbamoylpentyloxy, 6-carbamoylhexyloxy,1,1-dimethyl-2-carbamoylethoxy, 2-methyl-3-carbamoylpropoxy, and thelike.

The "hydroxy-substituted lower alkoxy" includes a straight chain orbranched chain alkoxy group having 1 to 6 carbon atoms and having 1 to 3hydroxy substitutents, for example, hydroxymethoxy, 2-hydroxyethoxy,1-hydroxyethoxy, 3-hydroxypropoxy, 2,3-dihydroxypropoxy,4-hydroxybutoxy, 3,4-dihydroxybutoxy, 1,1-dimethyl-2-hydroxyethoxy,5-hydroxypentyloxy, 6-hydroxyhexyloxy, 2-methyl-3-hydroxypropoxy,2,3,4-trihydroxybutoxy, and the like.

The "lower alkoxycarbonyl-substituted lower alkoxy" includes analkoxycarbonyl-substituted straight chain or branched chain alkoxy grouphaving 1 to 6 carbon atoms wherein the alkoxycarbonyl moiety is astraight chain or branched chain alkoxycarbonyl group having 1 to 6carbon atoms, for example, methoxycarbonylmethoxy,3-methoxycarbonylpropoxy, ethoxycarboxymethoxy, 3-ethoxycarbonylpropoxy,4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy,6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy,2-methyl-3-tertbutoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy,hexyloxycarbonylmethoxy, and the like.

The "carboxy-substituted lower alkoxy" includes a carboxy-substitutedalkoxy group wherein the alkoxy moiety is a straight chain or branchedchain alkoxy group having 1 to 6 carbon atoms, for example,carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy,4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy,1,1-dimethyl-2-carboxyethoxy, 2-methyl-3-carboxypropoxy, and the like.

The "phthalimido-substituted lower alkoxy" includes a straight chain orbranched chain alkoxy group having 1 to 6 carbon atoms which issubstituted by phthalimido group, for example, phthalimidomethoxy,2-phthalimidoethoxy, 1-phthalimidoethoxy, 3-phthalimidopropoxy,4-phthalimidobutoxy, 5-phthalimidopentyloxy, 6-phthalimidohexyloxy,1,1-dimethyl-2-phthalimidoethoxy, 2-methyl-3-phthalimidopropoxy, and thelike.

The "5- or 6-membered saturated heterocyclic group which is formed bybinding the groups R⁶ and R⁷ together with the nitrogen atom to whichthey bond with or without being intervened with nitrogen or oxygen atom"includes, for example, pyrrolidinyl, piperidinyl, piperazinyl,morpholino, and the like.

The "heterocyclic group having a substituent selected from piperidinyland a lower alkyl" includes a heterocyclic group having 1 to 3substituents selected from piperidinyl and a straight chain or branchedchain alkyl group having 1 to 6 carbon atoms, for example,4-methylpiperiazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl,2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl,3-pentylmorpholino, 4-hexylpiperazinyl, 4-(1-piperidinyl)piperidinyl,3-(1-piperidinyl)pyrrolidinyl, 3-(1-piperidinyl)-4-methylpiperazinyl,3-(1-piperidinyl)morpholino, and the like.

The "phenyl(lower)alkanoyl" includes a phenylalkanoyl wherein thealkanoyl moiety is a straight chain or branched chain alkanoyl grouphaving 2 to 6 carbon atoms, for example, phenylacetyl,3-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyryl,2,2-dimethyl-3-phenylpropionyl, 5-phenylpentanoyl, 6-phenylhexanoyl, andthe like.

The "cycloalkyl-lower alkanoyl" includes C₃ -C₈ cycloalkyl-alkanoylgroup wherein the alkanoyl moiety is a straight chain or branched chainalkanoyl having 2 to 6 carbon atoms, for example, cyclohexylacetyl,3-cyclopropylpropionyl, 2-cyclopentylpropionyl, 4-cyclohexylbutyryl,2,2-dimethyl-3-cycloheptylpropionyl, 5-cyclooctylpentanoyl,6-cyclohexylhexanoyl, and the like.

The "cycloalkylcarbonyl" includes a cycloalkylcarbonyl having 3 to 8carbon atoms, for example, cyclopropylcarbonyl, cyclobutylcarbonyl,cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl,cyclooctylcarbonyl, and the like.

The "amino having optionally a lower alkanoyl substituent" includes anamino having optionally a straight chain or branched chain alkanoylgroup having 1 to 6 carbon atoms, for example, amino, formylamino,acetylamino, propionylamino, butyrylamino, isobutyrylamino,pentanoylamino, tert-butylcarbonylamino, hexanoylamino, and the like.

The "phenoxy-lower alkanoyl which phenyl ring has optionally 1 to 3substituents selected from a lower alkyl, a lower alkoxy and an aminohaving optonally a lower alkanoyl substituent" includes aphenoxyalkanoyl group wherein the alkanoyl moiety is a straight chain orbranched chain alkanoyl having 2 to 6 carbon atoms and the phenyl ringhas optionally 1 to 3 substituents selected from a straight chain orbranched chain alkyl having 1 to 6 carbon atoms, a straight chain orbranched chain alkoxy having 1 to 6 carbon atoms and an amino havingoptionally a straight chain or branched chain alkanoyl having 1 to 6carbon atoms, for example, phenoxyacetyl, 3-phenoxypropionyl,2-phenoxypropionyl, 4-phenoxybutyryl, 2,2-dimethyl-3-phenoxypropionyl,5-phenoxypentanoyl, 6-phenoxyhexanoyl, (2-aminophenoxy)acetyl,3-(4-aminophenoxy)propionyl, (2-methylphenoxy)acetyl,(4-methylphenoxy)acetyl, (3-methylphenoxy)acetyl,(3-methoxyphenoxy)acetyl, (3-acetylaminophenoxy)acetyl,4-(2-propionylaminophenoxy)butyryl,2,2-dimethyl-3-(4-butyrylaminophenoxy)propionyl,5-(2-pentanoylaminophenoxy)pentanoyl,6-(4-hexanoylaminophenoxy)hexanoyl, 3-(2-ethylphenoxy)propionyl,2-(4-propylphenoxy)propionyl, 4-(4-butylphenoxy)butyryl,5-(3-pentylphenoxy)pentanoyl, 6-(4-hexylphenoxy)hexanoyl,(2,3-dimethylphenoxy)acetyl, (2,5-dimethylphenoxy)acetyl,(3,4-dimethylphenoxy)acetyl, (3,4,5-trimethylphenoxy)acetyl,3-(4-ethoxyphenoxy)propionyl, 2-(2-propoxyphenoxy)propionyl,4-(3-butoxyphenoxy)butyryl, 5-(4-pentyloxyphenoxy)pentanoyl,6-(4-hexyloxyphenoxy)hexanoyl, (3,4-dimethoxyphenoxy)acetyl,(3,5-dimethoxyphenoxy)acetyl, (2,4-dimethoxyphenoxy)acetyl,(3,4,5-trimethoxyphenoxy)acetyl, (2-acetylamino-4-methylphenoxy)acetyl,(4-acetylamino-3-methoxyphenoxy)acetyl, and the like.

The "phthalimido-substituted lower alkanoyl" includes a straight chainor branched chain alkanoyl group having 2 to 6 carbon atoms which issubstituted by phthalimido group, for example, 2-phthalimidoacetyl,3-phthalimidopropionyl, 2-phthalimidopropionyl, 4-phthalimidobutyryl,2,2-dimethyl-3-phthalimidopropionyl, 5-phthalimidopentanoyl,6-phthalimidohexanoyl, 3-methyl-4-phthalimidobutyryl, and the like.

The "lower alkoxycarbonyl-lower alkanoyl" includes analkoxycarbonyl-alkanoyl group wherein the alkoxy moiety is a straightchain or branched chain alkoxy having 1 to 6 carbon atoms and thealkanoyl moiety is a straight chain or branched chain alkanoyl having 2to 6 carbon atoms, for example, methoxycarbonylacetyl,3-methoxycarbonylpropionyl, ethoxycarbonylacetyl,3-ethoxycarbonylpropionyl, 4-ethoxycarbonylbutyryl,3-propoxycarbonylpropionyl, 2-methoxycarbonylpropionyl,6-propoxycarbonylhexanoyl, 5-isopropoxycarbonylpentanoyl,2,2-dimethyl-3-butoxycarbonylpropionyl,2-methyl-3-tert-butoxycarbonylpropionyl, pentyloxycarbonylacetyl,hexyloxycarbonylacetyl, and the like.

The "carboxy-lower alkanoyl" includes a carboxyalkanoyl group whereinthe alkanoyl moiety is a straight chain or branched chain alkanoylhaving 2 to 6 carbon atoms, for example, carboxyacetyl,3-carboxypropionyl, 2-carboxypropionyl, 4-carboxybutyryl,2,2-dimethyl-3-carboxypropionyl, 5-carboxypentanoyl, 6-carboxyhexanoyl,and the like.

The "naphthyloxy-lower alkanoyl" includes a naphthyloxy-alkanoyl groupwherein the alkanoyl moiety is a straight chain or branched chainalkanoyl having 2 to 6 carbon atoms, for example, naphtyloxyacetyl,3-naphtyloxypropionyl, 2-naphtyloxypropionyl, 4-naphthyloxybutyryl,2,2-dimethyl-3-naphthyloxypropionyl, 5-naphthyloxypentanoyl,6-naphthyloxyhexanoyl, and the like.

The "phenyl-lower alkoxycarbonyl" includes a phenylalkoxycarbonylwherein the alkoxycarbonyl moiety is a straight chain or branched chainalkoxycarbonyl group having 1 to 6 carbon atoms, for example,benzyloxycarbonyl, 2-phenylethoxycarbonyl, 1-phenylethoxycarbonyl,3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl,5-phenylpentyloxycarbonyl, 6-phenylhexyloxycarbonyl,1,1-dimethyl-2-phenylethoxycarbonyl, 2-methyl-3-phenylpropoxycarbonyl,and the like.

The "lower alkyl having optionally a hydroxy substituent" includes astraight chain or branched chain alkyl having 1 to 6 carbon atoms andhaving optionally 1 to 3 hydroxy substituents, for example,hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl,2,3-dihydroxyethyl, 4-hydroxybutyl, 3,4-dihydroxybutyl,1,1-dimethyl-2-hydroxyethyl, 5-hydroxypentyl, 6-hydroxyhexyl,2-methyl-3-hydroxypropyl, 2,3,4-trihydroxybutyl, and the like.

The "phenyl-lower alkyl" includes a phenylalkyl group wherein the alkylmoiety is a straight chain or branched chain alkyl group having 1 to 6carbon atoms, for example, benzyl, 2-phenylethyl, 1-phenylethyl,3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl,1,1-dimethyl-2-phenylethyl, 2-methyl-3-phenylpropyl, and the like.

The "phenoxy-lower alkyl" includes a phenoxyalkyl group wherein thealkyl moiety is a straight chain or branched chain alkyl group having 1to 6 carbon atoms, for example, phenoxymethyl, 1-phenoxyethyl,2-phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, 5-phenoxypentyl,6-phenoxyhexyl, 1,1-dimethyl-2-phenoxyethyl, 2-methyl-3-phenoxypropyl,and the like.

The "phenyl which has optionally 1 to 3 substituents selected from alower alkyl, a lower alkoxy and a halogen atom" includes a phenyl groupwhich has optionally 1 to 3 substituents selected from a straight chainor branched chain alkyl group having 1 to 6 carbon atoms, a straightchain or branched chain alkoxy group having 1 to 6 carbon atoms and ahalogen atom, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl,4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl,4-isopropoxyphenyl, 4-pentyloxyphenyl, 2,4-dimethoxyphenyl,4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl,2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5-dimethoxyphenyl,2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxyphenyl,3,4,5-trimethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl,2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl,3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl,3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl,2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl,3,5-dibromophenyl, 3,4,5-trichlorophenyl, 2-methoxy-3-chlorophenyl,2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl,3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl,4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl,2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl,3,4,5-trimethylphenyl, 3-chloro-4-methylphenyl,3-methoxy-4-methyl-5-iodophenyl, 3,4-dimethoxy-5-bromophenyl,3,5-diiodo-4-methoxyphenyl, and the like.

The "amino-lower alkyl having optionally a lower alkyl substituent"includes a straight chain or branched chain alkyl group having 1 to 6carbon atoms which is substituted by an amino group having optionally 1to 2 substituents of a straight chain or branched chain alkyl grouphaving 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl,1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl,1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl,1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl,4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl,dimethylaminomethyl, (N-ethyl-N-propylamino)methyl,2-(N-methyl-N-hexylamino)ethyl, and the like.

The "5- or 6-membered saturated heterocyclic group which is formed bybinding the groups R⁹ and R¹⁰ together with the nitrogen atom to whichthey bond with or without being intervened with nitrogen or oxygen atom"includes, for example, pyrrolidinyl, piperidinyl, piperazinyl,morpholino, and the like.

The "heterocyclic group having a substituent selected from a loweralkyl, a lower alkoxycarbonyl and piperidinyl" includes a heterocyclicgroup having 1 to 3 substituents selected from a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms, a straight chainor branched chain alkoxycarbonyl having 1 to 6 carbon atoms andpiperidinyl, for example, in addition to the above-mentionedheterocyclic groups having a substituent of a lower alkyl andpiperidinyl, 4-methoxycarbonylpiperazinyl, 4-ethoxycarbonylpiperidinyl,3-propoxycarbonylpyrrolidinyl, 2-pentyloxycarbonylmorpholino,4-hexyloxycarbonylpiperidinyl, 4-ethoxycarbonyl-3-methylpiperidinyl,3-methyl-4-ethoxycarbonylpiperazinyl, and the like.

The "5- or 6-membered saturated heterocyclic group which is formed bybinding the groups R¹⁴ and R¹⁵ together with the nitrogen atom to whichthey bond with or without being intervened with nitrogen or oxygen atom"includes, for example, pyrrolidinyl, piperidinyl, piperazinyl,morpholino, and the like.

The "heterocyclic group having a lower alkyl substituent" includes aheterocyclic group having 1 to 3 substituents of a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms, for example,4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl,2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl,3-pentylmorpholino, 4-hexylpiperazinyl, and the like.

The heterocyclic ring in the formula (1) includes tetrahydroquinolyl,2,3,4,5-tetrahydro-1H-benzazepinyl, 1,2,3,4,5,6-hexahydrobenzazocinyl,1,2-dihydroquinolyl, 2,3-dihydro-1H-benzazepinyl,1,2,3,4-tetrahydrobenzazocinyl, and the like.

The heterocyclic ring in the formula (1) wherein the carbon atom in thegroup of the formula: --(CH₂)_(p) -- or --CH═CH--(CH₂)_(q) -- for W isreplaced by oxygen atom, sulfur atom, sulfinyl, sulfonyl, or a group ofthe formula: ##STR15## (R¹³ is hydrogen atom or a lower alkyl) includesa heterocylic group wherein the carbon atom in the group of the formula:--(CH₂)_(p) -- or --CH═CH--(CH₂)_(q) -- for W is replaced by oxygenatom, sulfur atom, sulfinyl, sulfonyl, or a group of the formula:##STR16## (R¹³ is hydrogen atom or a straight chain or branched chainalkyl having 1 to 6 carbon atoms), for example,3,4-dihydro-2H-1,4-benzoxazinyl, 1,2,3,5-tetrahydro-4,1-benzoxazepinyl,1,2,3,4-tetrahydroquinoxalinyl,1,2,3,4,5,6-hexahydro-1,5-benzodiazocinyl,5-methyl-1,2,3,4,5,6-hexahydro-1,5-benzodiazocinyl,4-methyl-1,2,3,4-tetrahydroquinoxalinyl,1,2,3,4-tetrahydro-5,1-benzoxazepinyl,3,4-dihydro-2H-1,4-benzothiazinyl,2,3,4,5-tetrahydro-1,5-benzothiazepinyl,1,2,3,5-tetrahydro-4,1-benzothiazepinyl,4-ethyl-1,2,3,4-tetrahydroquinoxalinyl,4-propyl-1,2,3,4-tetrahydroquinoxalinyl,4-butyl-1,2,3,4-tetrahydroquinoxalinyl,4-pentyl-1,2,3,4-tetrahydroquinoxalinyl,4-hexyl-1,2,3,4-tetrahydroquinoxalinyl,2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-ethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-propyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-butyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-pentyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-hexyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-methyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-ethyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-propyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-butyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-pentyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-hexyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,3,4-dihydro-1-oxo-2H-1,4-benzothiazepinyl,3,4-dihydro-1,1-dioxo-2H-1,4-benzothiazepinyl,1-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepinyl,1,1-dioxo-2,3,4,5-tetrahydro-1,5-benzothiazepinyl,4-oxo-1,2,3,5-tetrahydro-4,1-benzothiazepinyl,4,4-dioxo-1,2,3,5-tetrahydro-4,1-benzothiazepinyl, and the like.

The "halogen-substituted lower alkoxy" includes a straight chain orbranched chain alkoxy group having 1 to 6 carbon atoms which has 1 to 3substituents of a halogen atom, for example, trifluoromethoxy,trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy,iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy,2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-chloropropoxy,2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy,5-chloropentyloxy, 3-chloro-2-methylpropoxy, 6-bromohexyloxy,5,6-dichlorohexyloxy, and the like.

The "halogen-substituted lower alkanoyl" includes a straight chain orbranched chain alkanoyl group having 1 to 6 carbon atoms which has 1 to3 substituents of a halogen atom, for example, 2,2,2-trifluoroacetyl,2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl,2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl,3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl,2,3-dichloropropionyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl,5-chloropentanoyl, 3-chloro-2-methylpropionyl, 6-bromohexanoyl,5,6-dibromohexanoyl, and the like.

The "aminocarbonyl-lower alkoxy having a lower alkyl substituent"includes a straight chain or branched chain alkoxy group having 1 to 6carbon atoms which is substituted by an aminocarbonyl group having 1 to2 substituents of a straight chain or branched chain alkyl group having1 to 6 carbon atoms, for example, methylaminocarbonylmethoxy,1-ethylaminocarbonylethoxy, 2-propylaminocarbonylethoxy,3-isopropylaminocarbonylpropoxy, 4-butylaminocarbonylbutoxy,5-pentylaminocarbonylpentyloxy, 6-hexylaminocarbonylhexyloxy,dimethylaminocarbonylmethoxy, 3-diethylaminocarbonylpropoxy,diethylaminocarbonylmethoxy, (N-ethyl-N-propylamino)carbonylmethoxy,2-(N-methyl-N-hexylamino)carbonylethoxy, and the like.

The "carbamoyl-lower alkyl" includes a carbamoyl-substituted alkyl groupwherein the alkyl moiety is a straight chain or branched chain alkylgroup having 1 to 6 carbon atoms, for example, carbamoylmethyl,2-carbamoylethyl, 1-carbamoylethyl, 3-carbamoylpropyl, 4-carbamoylbutyl,5-carbamoylpentyl, 6-carbamoylhexyl, 1,1-dimethyl-2-carbamoylethyl,2-methyl-3-carbamoylpropyl, and the like.

The "amino-lower alkanoyl having optionally a lower alkyl substituent"includes a straight chain or branched chain alkanoyl having 2 to 6carbon atoms which is substituted by an amino group having optionally 1to 2 substituents of a straight chain or branched chain alkyl grouphaving 1 to 6 carbon atoms, for example, 2-aminoacetyl,3-aminopropionyl, 2-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl,6-aminohexanoyl, 2,2-dimethyl-3-aminopropionyl,2-methyl-3-aminopropionyl, 2-methylaminoacetyl, 2-ethylaminopropionyl,3-propylaminopropionyl, 3-isopropylaminopropionyl, 4-butylaminobutyryl,5-pentylaminopentanoyl, 6-hexylaminohexanoyl, 2-dimethylaminoacetyl,2-diethylaminoacetyl, 2-(N-ethyl-N-propylamino)acetyl,3-(N-methyl-N-hexylamino)propionyl, and the like.

The "amino-lower alkyl having optionally a lower alkanoyl substituent"includes a straight chain or branched chain alkyl having 1 to 6 carbonatoms which is substituted by an amino group having optionally asubstituent of a straight chain or branched chain alkanoyl group having1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl,1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl,1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, acetylaminomethyl,1-acetylaminoethyl, 2-propionylaminoethyl, 3-isopropionylaminopropyl,4-butyrylaminobutyl, 5-pentanoylaminopentyl, 6-hexanoylaminohexyl,formylaminomethyl, and the like.

The "anilinocarbonyl having optionally a lower alkyl substituent on thephenyl ring" includes an anilinocarbonyl group having optionally 1 to 3substituents of a straight chain or branched chain alkyl group having 1to 6 carbon atoms on the phenyl ring, for example, anilinocarbonyl,2-methylanilinocarbonyl, 3-methylanilinocarbonyl,4-methylanilinocarbonyl, 2-ethylanilinocarbonyl, 3-ethylanilinocarbonyl,4-ethylanilinocarbonyl, 4-isopropylanilinocarbonyl,3-butylanilinocarbonyl, 4-pentylanilinocarbonyl, 4-hexylanilinocarbonyl,3,4-dimethylanilinocarbonyl, 3,4-diethylanilinocarbonyl,2,4-dimethylanilinocarbonyl, 2,5-dimethylanilinocarbonyl,2,6-dimethylanilinocarbonyl, 3,4,5-trimethylanilinocarbonyl, and thelike.

The "phenylsulfonyl which has optionally a substituent selected from ahalogen and a lower alkyl on the phenyl ring" includes a phenylsulfonylgroup which has optionally 1 to 3 substitutents selected from a straightchain or branched chain alkyl group having 1 to 6 carbon atoms and ahalogen atom, for example, phenylsulfonyl, 2-chlorophenylsulfonyl,3-chlorophenylsulfonyl, 4-chlorophenylsulfonyl, 2-fluorophenylsulfonyl,3-fluorophenylsulfonyl, 4-fluorophenylsulfonyl, 2-bromophenylsulfonyl,3-bromophenylsulfonyl, 4-bromophenylsulfonyl, 2-iodophenylsulfonyl,3-iodophenylsulfonyl, 4-iodophenylsulfonyl, 3,4-dichlorophenylsulfonyl,3,5-dichlorophenylsulfonyl, 2,6-dichlorophenylsulfonyl,2,3-dichlorophenylsulfonyl, 2,4-dichlorophenylsulfonyl,3,4-difluorophenylsulfonyl, 3,5-dibromophenylsulfonyl,3,4,5-trichlorophenylsulfonyl, 2-ethyl-3-chlorophenylsulfonyl,2-methylphenylsulfonyl, 3-methylphenylsulfonyl, 4-methylphenylsulfonyl,2-ethylphenylsulfonyl, 3-ethylphenylsulfonyl, 4-ethylphenylsulfonyl,4-isopropylphenylsulfonyl, 3-butylphenylsulfonyl,4-pentylphenylsulfonyl, 4-hexylphenylsulfonyl,3,4-dimethylphenylsulfonyl, 3,4-diethylphenylsulfonyl,2,4-dimethylphenylsulfonyl, 2,5-dimethylphenylsulfonyl,2,6-dimethylphenylsulfonyl, 3,4,6-trimethylphenylsulfonyl,3,4,5-trimethylphenylsulfonyl, 3-chloro-4-methylphenylsulfonyl,4-methyl-5-iodophenylsulfonyl, 3,4-dimethyl-5-bromophenylsulfonyl,3,5-diiodo-4-methylphenylsulfonyl, and the like.

The "phthalimido-substituted lower alkyl" includes a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms which issubstituted by phthalimido group, for example, phthalimidomethyl,2-phthalimidoethyl, 1-phthalimidoethyl, 3-phthalimidopropyl,4-phthalimidobutyl, 5-phthalimidopentyl, 6-phthalimidohexyl,1,1-dimethyl-2-phthalimidoethyl, 2-methyl-3-phthalimidopropyl, and thelike.

The "lower alkynyl" includes a straight chain or branched chain alkynylhaving 2 to 6 carbon atoms, for example, ethynyl, 2-propynyl, 2-butynyl,3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, 2-hexynyl, and the like.

The "benzoyl which has optionally a halogen substituent on the phenylring" includes a benzoyl group which has optionally 1 to 3 substituentsof a halogen atom on the phenyl ring, for example, benzoyl,2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-fluorobenzoyl,3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 3-bromobenzoyl,4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 4-iodobenzoyl,3,4-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,6-dichlorobenzoyl,2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 3,4-difluorobenzoyl,3,5-dibromobenzoyl, 3,4,5-trichlorobenzoyl, and the like.

The "phenyl-lower alkoxy" includes a phenylalkoxy group wherein thealkoxy moiety is a straight chain or branched chain alkoxy group having1 to 6 carbon atoms, for example, benzyloxy, 2-phenylethoxy,1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy,6-phenylhexyloxy, 1,1-dimethyl-2-phenylethoxy, 2-methyl-3-phenylpropoxy,and the like.

The "amino-lower alkoxy having optionally a substituent selected from alower alkyl and a lower alkanoyl" include a straight chain or branchedchain alkoxy group having 1 to 6 carbon atoms which is substituted by anamino group having optionally 1 to 2 substituents selected from astraight chain or branched chain alkyl group having 1 to 6 carbon atomsand a straight chain or branched chain alkanoyl group having 1 to 6carbon atoms, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy,3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy,1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, acetylaminomethoxy,1-acetylaminoethoxy, 2-propionylaminoethoxy, 3-isopropionylaminopropoxy,4-butyrylaminobutoxy, 5-pentanoylaminopentyloxy,6-hexanoylaminohexyloxy, formylaminomethoxy, methylaminomethoxy,1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy,4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy,dimethylaminomethoxy, (N-ethyl-N-propylamino)methoxy,2-(N-methyl-N-hexylamino)ethoxy, and the like.

The "benzoyloxy which has optionally a halogen substituent on the phenylring" includes a benzoyloxy group which has optionally 1 to 3substituents of a halogen atom on the phenyl ring, for example,benzoyloxy, 2-chlorobenzoyloxy, 3-chlorobenzoyloxy, 4-chlorobenzoyloxy,2-fluorobenzoyloxy, 3-fluorobenzoyloxy, 4-fluorobenzoyloxy,2-bromobenzoyloxy, 3-bromobenzoyloxy, 4-bromobenzoyloxy,2-iodobenzoyloxy, 3-iodobenzoyloxy, 4-iodobenzoyloxy,3,4-dichlorobenzoyloxy, 3,5-dichlorobenzoyloxy, 2,6-dichlorobenzoyloxy,2,3-dichlorobenzoyloxy, 2,4-dichlorobenzoyloxy, 3,4-difluorobenzoyloxy,3,5-dibromobenzoyloxy, 3,4,5-trichlorobenzoyloxy, and the like.

The "lower alkanoyloxy-substituted lower alkyl" includes a straightchain or branched chain alkyl group having 1 to 6 carbon atoms which issubstituted by a straight chain or branched chain alkanoyloxy grouphaving 2 to 6 carbon atoms, for example, acetyloxymethyl,2-propionyloxyethyl, 1-butyryloxyethyl, 3-acetyloxypropyl,4-acetyloxybutyl, 4-isobutyryloxybutyl, 5-pentanoyloxypentyl,6-acetyloxyhexyl, 6-tert-butylcarbonyloxyhexyl,1,1-dimethyl-2-hexanoyloxyethyl, 2-methyl-3-acetyloxypropyl, and thelike.

The "lower alkylsulfonyloxy-lower alkyl" includes a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms which issubstituted by a straight chain or branched chain alkylsulfonyloxy grouphaving 1 to 6 carbon atoms, for example, methylsulfonyloxymethyl,1-ethylsulfonyloxyethyl, 2-propylsulfonyloxyethyl,3-isopropylsulfonyloxypropyl, 4-butylsulfonyloxybutyl,5-pentylsulfoyloxypentyl, 6-hexylsulfonyloxyhexyl,1,1-dimethyl-2-methylsulfoyloxyethyl, 2-methyl-3-ethylsulfonyloxypropyl,and the like.

The "azido-lower alkyl" includes a straight chain or branched chainalkyl group having 1 to 6 carbon atoms which is substituted by an azidogroup, for example, azidomethyl, 1-azidoethyl, 2-azidoethyl,3-azidopropyl, 4-azidobutyl, 5-azidopentyl, 6-azidohexyl,1,1-dimethyl-2-azidoethyl, 2-methyl-3-azidopropyl, and the like.

The "lower alkanoyloxyimino" includes a straight chain or branched chainalkanoyloxyimino group having 1 to 6 carbon atoms, for example,formyloxyimino, acetyloxyimino, propionyloxyimino, butyryloxyimino,isobutyryloxyimino, pentanoyloxyimino, tert-butylcarbonyloxyimino,hexanoyloxyimino, and the like.

The "lower alkylidene" includes a straight chain or branched chainalkylidene group having 1 to 6 carbon atoms, for example, methylidene,ethylidene, propylidene, isopropylidene, butylidene, pentylidene,hexylidene, and the like.

The "oxiranyl-substituted lower alkyl" includes a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms which issubstituted by oxiranyl group, for example, oxiranylmethyl,1-oxiranylethyl, 2-oxiranylethyl, 3-oxiranylpropyl, 4-oxiranylbutyl,5-oxiranylpentyl, 6-oxiranylhexyl, 1,1-dimethyl-2-oxiranylethyl,2-methyl-3-oxiranylpropyl, and the like.

The "lower alkyl having 1 to 2 substituents selected from a loweralkoxy, hydroxy and an amino having optionally a lower alkylsubstituent" includes a straight chain or branched chain alkyl grouphaving 1 to 6 carbon atoms and having 1 to 2 substituents selected froma straight chain or branched chain alkoxy group having 1 to 6 carbonatoms, hydroxy and an amino having optionally a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms, for example,methoxymethyl, 1-ethoxyethyl, 2-propoxyethyl, 3-isopropoxypropyl,4-butoxybutyl, 5-pentyloxypentyl, 6-hexyloxyhexyl,1,1-dimethyl-2-methoxyethyl, 2-methyl-3-ethoxypropyl,3-methoxy-2-hydroxypropyl, hydroxymethyl, 2-hydroxyethyl,1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxyethyl, 4-hydroxybutyl,3,4-dihydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,6-dihydroxyhexyl,5-hydroxypentyl, 6-hydroxyhexyl,6-(N-ethyl-N-methylamino)-5-methoxyhexyl, 2-methyl-3-hydroxypropyl,aminomethyl, 1-aminoethyl, 2-aminoethyl, 3-aminopropyl, 4-aminobutyl,5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl,2-methyl-3-aminopropyl, methylaminomethyl, ethylaminomethy,propylaminomethyl, isopropylaminomethyl, butylaminomethyl,tert-butylaminomethyl, pentylaminomethyl, hexylaminomethyl,dimethylaminomethyl, diethylaminomethyl, dipropylaminomethyl,dibutylaminomethyl, dipentylaminomethyl, dihexylaminomethyl,N-methyl-N-ethylaminomethyl, N-methyl-N-propylaminomethyl,N-methyl-N-butylaminomethyl, N-methyl-N-hexylaminomethyl,1-methylaminoethyl, 2-ethylaminoethyl, 3-propylaminopropyl,4-butylaminobutyl, 1,1-dimethyl-2-pentylaminoethyl, 5-hexylaminopentyl,6-dimethylaminohexyl, 4-dimethylaminobutyl, 2-diethylaminoethyl,1-(N-methyl-N-hexylamino)ethyl, 3-dihexylaminopropyl,6-diethylaminohexyl, 4-dibutylaminobutyl,2-(N-methyl-N-pentylamino)ethyl, 2-hydroxy-3-diethylaminopropyl,3-hydroxy-4-methylaminobutyl, 5-hydroxy-6-diethylaminohexyl,4-hydroxy-5-dimethylaminopentyl, 4-hydroxy-5-methylaminopentyl,4-hydroxy-5-diethylaminopentyl, 5-hydroxy-6-ethylaminohexyl,5-hydroxy-6-isopropylaminohexyl, 5-hydroxy-6-aminohexyl, and the like.

The "aminocarbonyloxy having optionally a lower alkyl substituent"includes an aminocarbonyloxy group having optionally 1 to 2 substituentsof a straight chain or branched chain alkyl group having 1 to 6 carbonatoms, for example, aminocarbonyloxy, methylaminocarbonyloxy,ethylaminocarbonyloxy, propylaminocarbonyloxy,isopropylaminocarbonyloxy, butylaminocarbonyloxy,tert-butylaminocarbonyloxy, pentylaminocarbonyloxy,hexylaminocarbonyloxy, dimethylaminocarbonyloxy,diethylaminocarbonyloxy, dipropylaminocarbonyloxy,dibutylaminocarbonyloxy, dipentylaminocarbonyloxy,dihexylaminocarbonyloxy, N-methyl-N-ethylaminocarbonyloxy,N-ethyl-N-propylaminocarbonyloxy, N-methyl-N-butylaminocarbonyloxy,N-methyl-N-hexylaminocarbonyloxy, and the like.

The "lower alkanoyloxy having optionally a halogen substituent" includesa straight chain or branched chain alkanoyloxy group having 1 to 6carbon atoms which has optionally 1 to 3 substituents of a halogen atom,for example, in addition to the above lower alkanoyl group,2,2,2-trifluoroacetyloxy, 2,2,2-trichloroacetyloxy, 2-chloroacetyloxy,2-bromoacetyloxy, 2-fluoroacetyloxy, 2-iodoacetyloxy,2,2-difluoroacetyloxy, 2,2-dibromoacetyloxy,3,3,3-trifluoropropionyloxy, 3,3,3-trichloropropionyloxy,3-chloropropionyloxy, 2,3-dichloropropionyloxy,4,4,4-trichlorobutyryloxy, 4-fluorobutyryloxy, 5-chloropentanoyloxy,3-chloro-2-methylpropionyloxy, 6-bromohexanoyloxy,5,6-dibromohexanoyloxy, and the like.

The "amino-lower alkyl having optionally a substituent selected from alower alkyl and a lower alkanoyl" include a straight chain or branchedchain alkyl group having 1 to 6 carbon atoms which is substituted by anamino group having optionally 1 to 2 substituents selected from astraight chain or branched chain alkyl group having 1 to 6 carbon atomsand a straight chain or branched chain alkanoyl group having 1 to 6carbon atoms, for example, aminomethyl, 2-aminoethyl, 1-aminoethyl,3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl,1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, acetylaminomethyl,1-acetylaminoethyl, 2-propionylaminoethyl, 3-isopropionylaminopropyl,4-butyrylaminobutyl, 5-pentanoylaminopentyl, 6-hexanoylaminohexyl,formylaminomethyl, methylaminomethyl, 1-ethylaminoethyl,2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl,5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl,(N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, and thelike.

The "amino-lower alkanoyloxy having optionally a lower alkylsubstituent" includes a straight chain or branched chain alkanoyloxyhaving 2 to 6 carbon atoms which is substituted by an amino group havingoptionally 1 to 2 substituents of a straight chain or branched chainalkyl group having 1 to 6 carbon atoms, for example, 2-aminoacetyloxy,3-aminopropionyloxy, 2-aminopropionyloxy, 4-aminobutyryloxy,5-aminopentanoyloxy, 6-aminohexanoyloxy,2,2-dimethyl-3-aminopropionyloxy, 2-methyl-3-aminopropionyloxy,2-methylaminoacetyloxy, 2-ethylaminopropionyloxy,3-propylamninopropionyloxy, 3-isopropylaminopropionyloxy,4-butylaminobutyryloxy, 5-pentylaminopentanoyloxy,6-hexylaminohexanoyloxy, 2-dimethylaminoacetyloxy,2-diethylaminoacetyloxy, 2-(N-ethyl-N-propylamino)acetyloxy,3-(N-methyl-N-hexylamino)propionyloxy, and the like.

The "pyridyl-lower alkyl" include a pyridylalkyl group wherein the alkylmoiety is a straight chain or branched chain alkyl group having 1 to 6carbon atoms, for example, (4-pyridyl)methyl, 1-(3-pyridyl)ethyl,2-(2-pyridyl)ethyl, 3-(2-pyridyl)propyl, 4-(3-pyridyl)butyl,5-(4-pyridyl)pentyl, 6-(2-pyridyl)hexyl,1,1-dimethyl-2-(3-pyridyl)ethyl, 2-methyl-3-(4-pyridyl)propyl, and thelike.

The "5- or 6-membered saturated heterocyclic group which is formed bybinding the groups R⁸² and R⁸³ together with the nitrogen atom to whichthey bond with or without being intervened with nitrogen, oxygen orsulfur atom" includes, for example, pyrrolidinyl, piperidinyl,piperazinyl, morpholino, thiomorpholino, and the like.

The above heterocyclic group which has a substituent selected from oxo,a lower alkyl, a lower alkanoyl and carbamoyl includes the aboveheterocyclic groups which have 1 to 3 substituents selected from oxo, astraight chain or branched chain alkyl group having 1 to 6 carbon atoms,a straight chain or branched chain alkanoyl group having 1 to 6 carbonatoms, and carbamoyl group, for example, 4-methylpiperazinyl,3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl,3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino,4-hexylpiperazinyl, 2-methylthiomorpholino, 4-acetylpiperazinyl,2-propionylmorpholino, 3-butyrylthiomorpholino, 3-pentanoylpyrrolidinyl,4-hexanoylpiperidinyl, 3-methyl-4-acetylpiperazinyl,2-carbamoylpyrrolidinyl, 4-carbamoylpiperazinyl,3-carbamoylthiomorpholino, 2-carbamoylmorpholino,3-carbamoylpiperidinyl, 1-oxo-thiomorpholino, 1,1-dioxothiomorpholino,and the like.

The "lower alkylsulfonyl" includes a straight chain or branched chainalkylsulfonyl group having 1 to 6 carbon atoms, for example,methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl,butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, andthe like.

The "aminocarbonyl having optionally a lower alkyl substituent" includesan aminocarbonyl group having optionally 1 to 2 substituents of astraight chain or branched chain alkyl group having 1 to 6 carbon atoms,for example, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl,propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl,tert-butylaminocarbonyl, pentylaminocarbonyl, hexylaminocarbonyl,dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl,dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl,N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylaminocarbonyl,N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylaminocarbonyl, and thelike.

The "cyano-substituted lower alkyl" includes a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms which issubstituted by cyano group, for example, cyanomethyl, 2-cyanoethyl,1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl,1,1-dimethyl-2-caynoethyl, 2-methyl-3-cyanopropyl, and the like.

The "lower alkoxycarbonyl-substituted lower alkyl" includes analkoxycarbonyl-substituted straight chain or branched chain alkyl grouphaving 1 to 6 carbon atoms wherein the alkoxycarbonyl moiety is astraight chain or branched chain alkoxycarbonyl group having 1 to 6carbon atoms, for example, methoxycarbonylmethyl,3-methoxycarbonylpropyl, ethoxycarboxymethyl, 3-ethoxycarbonylpropyl,4-ethoxycarbonylbutyl, 5-isopropoxycarbonylpentyl,6-propoxycarbonylhexyl, 1,1-dimethyl-2-butoxycarbonylethyl,2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl,hexyloxycarbonylmethyl, and the like.

The "carboxy-substituted lower alkyl" includes a carboxy-substitutedalkyl group wherein the alkyl moiety is a straight chain or branchedchain alkyl group having 1 to 6 carbon atoms, for example,carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl,4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl,1,1-dimethyl-2-carboxyethyl, 2-methyl-3-carboxypropyl, and the like.

The "tetrahydropyranyloxy-substituted lower alkyl" includes atetrahydropyranyloxy-substituted straight chain or branched chain alkylgroup having 1 to 6 carbon atoms, for example,(2-tetrahydropyranyloxy)methyl, 2-(3-tetrahydropyranyloxy)ethyl,1-(4-tetrahydropyranyloxy)ethyl, 3-(2-tetrahydropyranyloxy)propyl,4-(3-tetrahydropyranyloxy)butyl, 5-(4-tetrahydropyranyloxy)pentyl,6-(2-tetrahydropyranyloxy)hexyl,1,1-dimethyl-2-(3-tetrahydropyranyloxy)ethyl,2-methyl-3-(4-tetrahydropyranyloxy)propyl, and the like.

The "piperidinyl having optionally a phenyl-lower alkyl substituent"includes a piperidinyl which has optionally a substituent of aphenylalkyl group wherein the alkyl moiety is a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms, for example,piperidinyl, 1-benzyl-4-piperidinyl, 1-(2-phenylethyl)-3-piperidinyl,1-(1-phenylethyl)-2-piperidinyl, 1-(3-phenylpropyl)-4-piperidinyl,1-(4-phenylbutyl)-4-piperidinyl, 1-(5-phenylpentyl)-4-piperidinyl,1-(6-phenylhexyl)-4-piperidinyl,1-(1,1-dimethyl-2-phenylethyl)-3-piperidinyl,1-(2-methyl-3-phenylpropyl)-2-piperidinyl, and the like.

The "imidazolyl-substituted lower alkanoyl" includes animidazolyl-substituted alkanoyl group wherein the alkanoyl moiety is astraight chain or branched chain alkanoyl group having 2 to 6 carbonatoms, for example, (1-imidazolyl)acetyl, 3-(2-imidazolyl)propionyl,2-(4-imidazolyl)propionyl, 4-(1-imidazolyl)butyryl,2,2-dimethyl-3-(2-imidazolyl)propionyl, 5-(4-imidazolyl)pentanoyl,6-(1-imidazolyl)hexanoyl, and the like.

The "amino-lower alkanoyl having optionally a substituent selected froma lower alkyl and a lower alkoxycarbonyl" includes a straight chain orbranched chain alkanoyl having 2 to 6 carbon atoms which is substitutedby an amino group having optionally 1 to 2 substituents selected from astraight chain or branched chain alkyl group having 1 to 6 carbon atomsand a straight chain or branched chain alkoxycarbonyl group having 1 to6 carbon atoms, for example, 2-aminoacetyl, 3-aminopropionyl,2-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl, 6-aminohexanoyl,2,2-dimethyl-3-aminopropionyl, 2-methyl-3-aminopropionyl,2-methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl,3-isopropylaminopropionyl, 4-butylaminobutyryl, 5-pentylaminopentanoyl,6-hexylaminohexanoyl, 2-dimethylaminoacetyl, 2-diethylaminoacetyl,2-(N-ethyl-N-propylamino)acetyl, 3-(N-methyl-N-hexylamino)propionyl,2-methoxycarbonylaminoacetyl, 2-ethoxycarbonylaminoacetyl,3-propoxycarbonylaminopropionyl, 4-butoxycarbonylaminobutyryl,2-tert-butoxycarbonylaminoacetyl, 5-pentyloxycarbonylaminopentanoyl,6-hexyloxycarbonylaminohexanoyl,2-(N-methyl-N-tert-butoxycarbonylamino)acetyl, and the like.

The "aminocarbonyl-lower alkyl having a lower alkyl substituent"includes a straight chain or branched chain alkyl group having 1 to 6carbon atoms which is substituted by an aminocarbonyl group having 1 to2 substituents of a straight chain or branched chain alkyl group having1 to 6 carbon atoms, for example, methylaminocarbonylmethyl,1-ethylaminocarbonylethyl, 2-propylaminocarbonylethyl,3-isopropylaminocarbonylpropyl, 4-butylaminocarbonylbutyl,5-pentylaminocarbonylpentyl, 6-hexylaminocarbonylhexyl,dimethylaminocarbonylmethyl, 3-diethylaminocarbonylpropyl,diethylaminocarbonylmethyl, (N-ethyl-N-propylamino)carbonylmethyl,2-(N-methyl-N-hexylamino)carbonylethyl, and the like.

The "amino-substituted lower alkoxy having optionally a lower alkylsubstituent" includes an amino-substituted straight chain or branchedchain alkoxy having 1 to 6 carbon atoms which has optionally 1 to 2substituents of a straight chain or branched chain alkyl having 1 to 6carbon atoms, such as aminomethoxy, 2-aminoethoxy, 1-aminoethoxy,3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy,1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, methylaminomethoxy,1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy,4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy,dimethylaminomethoxy, (N-ethyl-N-propylamino)methoxy,2-(N-methyl-N-hexylamino)ethoxy, and the like.

The compounds of the present invention can be prepared by variousprocesses, for example, by the processes shown in the following reactionschemes. ##STR17## wherein R¹, R², R³, and W are the same as definedabove.

The process of Reaction Scheme-1 is carried out by reacting abenzoheterocyclic compound of the formula (2) and a carboxylic acidcompound of the formula (3) by a conventional amido bond formingreaction. The amido bond forming reaction can be carried out under theconditions for the conventional amido bond forming reaction, forexample,

(a) a mixed acid anhydride process, i.e. a process of reacting thecarboxylic acid compound (3) with an alkylhalocarboxylic acid to form amixed acid anhydride and reacting the resultant with the amine compound(2),

(b) an activated ester process, i.e. a process of converting thecarboxylic acid compound (3) into an activated ester, such asp-nitrophenyl ester, N-hydroxysuccinimide ester, 1-hydroxybenzotriazoleester, etc., and reacting the resultant with the amine compound (2),

(c) a carbodiimide process, i.e. a process of condensing the carboxylicacid compound (3) and the amine compound (2) in the presence of anactivating agent such as dicyclohexylcarbodiimide, carbonyldiimidazole,etc.,

(d) other processes, i.e. a process of converting the carboxylic acidcompound (3) into a carboxylic anhydride by treatment with a dehydratingagent such as acetic anhydride, and reacting the resultant with theamine compound (2); a process of reacting an ester of the carboxylicacid compound (3) with a lower alcohol and the amine compound (2) at ahigh temperature under high pressure; a process of reacting an acidhalide compound of the carboxylic acid compound (3), i.e. a carboxylicacid halide, with the amine compound (2), and the like.

The mixed acid anhydride used in the above mixed acid anhydride process(a) is obtained by the known Schotten-Baumann reaction, and the reactionproduct is used without isolation from the reaction mixture for thereaction with the amine compound (2) to give the desired compound of theformula (1). The Schotten-Baumann reaction is usually carried out in thepresence of a basic compound. The basic compound is any conventionalcompounds used for the Schotten-Baumann reaction and includes, forexample, organic basic compounds such as triethylamine, trimethylamine,pyridine, dimethylaniline, N-methylmorpholine,1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7(DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), etc., and inorganic basiccompounds such as potassium carbonate, sodium carbonate, potassiumhydrogen carbonate, sodium hydrogen carbonate, etc. The reaction isusually carried out at a temperature of from about -20° C. to about 100°C., preferably from about 0° C. to about 50° C., for about 5 minutes toabout 10 hours, preferably about 5 minutes to about 2 hours.

The reaction of the thus obtained mixed acid anhydride with the aminecompound (2) is usually carried out at a temperature of from about -20°C. to about 150° C., preferably about 10° C. to about 50° C., for about5 minutes to about 10 hours, preferably about 5 minutes to about 5hours. The mixed acid anhydride process is usually carried out in anappropriate solvent. The solvent is any conventional solvents which areusually used in the mixed acid anhydride process and includes, forexample, halogenated hydrocarbons (e.g. chloroform, dichloromethanedichloroethane, etc.), aromatic hydrocarbons (e.g. benzene, toluene,xylene, etc.), ethers (e.g. diethyl ether, diisopropyl ether,tetrahydrofuran, dimethoxyethane, etc.), esters (e.g. methyl acetate,ethyl acetate, etc.), aprotic polar solvents (e.g.N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide,etc.), or a mixture of these solvents. The alkylhalocarboxylic acid usedin the mixed acid anhydride process includes, for example, methylchloroformate, methyl bromoformate, ethyl chloroformate, ethylbromoformate, isobutyl chloroformate, and the like. In said process, thecarboxylic acid compound (3), the alkylhalocarboxylic acid and the amine(2) are usually used in each equimolar amount, but preferably, thealkylhalocarboxylic acid and the carboxylic acid compound (3) are usedeach in an amount of about 1 to 1.5 mole to 1 mole of the amine (2).

Among the above other processes (d), in case of the process of reactingthe carboxylic acid halide with the amine compound (2), the reaction isusually carried out in the presence of a basic compound in anappropriate solvent. The basic compound is any conventional compoundsand includes, in addition to the basic compounds used for theabove-mentioned Schotten-Baumann reaction, sodium hydroxide, potassiumhydroxide, sodium hydride, potassium hydride. etc. The solvent includes,in addition to the solvents used for the above-mentioned mixed acidanhydride process, alcohols (e.g. methanol, ethanol, propanol, butanol,3-methoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.),acetonitrile, pyridine, acetone, water, and the like. The amount of theamine compound (2) and the carboxylic acid halide is not critical, butthe carboxylic acid halide is usually used at least in equimolar amount,preferably about 1 to 5 moles to 1 mole of the amine compound (2). Thereaction is usually carried out at a temperature of from about -20° C.to about 180° C., preferably from about 0° C. to about 150° C., forabout 5 minutes to about 30 hours.

The amido bond forming reaction in the above Reaction Scheme-1 may alsobe carried out by reacting the carboxylic acid compound (3) and theamine (2) in the presence of a condensation agent, i.e. phosphoriccompounds such as triphenylphosphine, diphenylphosphinyl chloride,phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate,diethyl phosphorocyanidate, diphenylphosphoric azide,bis(2-oxo-3-oxazolidinyl)phosphinic chloride, etc. The reaction isusually carried out in the presence of the solvent and basic compound asused in the above reaction of the carboxylic acid halide and the amine(2) at a temperature of from about -20° C. to about 150° C., preferablyabout 0° C. to about 100° C., for about 5 minutes to about 30 hours. Thecondensation agent and the carboxylic acid compound (3) are used atleast in equimolar amount, preferably about 1 to 2 moles, to 1 mole ofthe amine (2). ##STR18## wherein R¹, R², R⁴ and W are as defined above,R^(5a) is the same as R⁵ as defined above except excluding ananilinocarbonyl having optionally a lower alkyl substituent on thephenyl ring, a phenylsulfonyl having optionally a substituent selectedfrom a halogen atom and a lower alkyl on the phenyl ring andquinolylsulfonyl.

The reaction of the compound (2b) and the compound (4) is carried out inthe same manner as in the reaction of the compound (2) and the compound(3) in the above Reaction Scheme-1. ##STR19## wherein R¹, R², R¹¹, R¹²and W are as defined above.

The reaction of the compound (5) and the compound (6) is carried outunder the same conditions as used in the reaction of the compound (2)and the compound (3) in the above Reaction Scheme-1. ##STR20## whereinR¹, R², R⁵ and W are as defined above, and R^(4a) is a lower alkyl, R¹⁷and R¹⁸ are each hydrogen atom or a lower alkyl, and X is a halogenatom.

The reaction of the compound (7) and the compound (8) is usually carriedout in an inert solvent in the presence or absence of a basic compound.The inert solvent includes, for example, aromatic hydrocarbons (e.g.benzene, toluene, xylene, etc.), ethers (e.g. tetrahydrofuran, dioxane,diethylene glycol dimethyl ether, etc.), halogenated hydrocarbons (e.g.dichloromethane, chloroform, carbon tetrachloride, etc.), lower alcohols(e.g. methanol, ethanol, isopropanol, butanol, tert-butanol, etc.),acetic acid, ethyl acetate, acetone, acetonitrile, pyridine,dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide,etc., or a mixture of these solvents. The basic compound includes, forexample, carbonates (e.g. sodium carbonate, potassium carbonate, sodiumhydrogen carbonate, potassium hydrogen carbonate, etc.), metalhydroxides (e.g. sodium hydroxide, potassium hydroxide, etc.), sodiumhydride, potassium, sodium, sodium amide, metal alcoholates (e.g. sodiummethoxide, sodium ethoxide, etc.), and organic basic compounds (e.g.pyridine, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine,1,5-diazabicyclo[4.3.0]nonene-(5) (DBN),1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane(DABCO), etc.). The amount of the compound (7) and the compound (8) isnot critical, but the compound (8) is usually used at least inequivalent amount, preferably 1 to 10 moles, to 1 mole of the compound(7). The reaction is usually carried out at a temperature of from about0° C. to about 200° C., preferably from about 0° C. to about 170° C.,for about 30 minutes to about 30 hours. In the reaction, an alkali metalhalide (e.g. sodium iodide, potassium iodide, etc.) may be added to thereaction system.

The reaction of the compound (7) and the compound (9) is carried out inan appropriate solvent or without solvent in the presence of a reducingagent. The solvent includes, for example, water, alcohols (e.g.methanol, ethanol, isopropanol, etc.), acetonitrile, formic acid, aceticacid, ethers (e.g. dioxane, diethyl ether, diglyme, tetrahydrofuran,etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or amixture of these solvents. The reducing agent includes, for example,formic acid, fatty acid alkali metal salts (e.g. sodium formate, etc.),hydrogenating reducing agents (e.g. sodium boro hydride, sodiumcyanoboro hydride, lithium aluminum hydride, etc.), catalystic reducingagents (e.g. palladium black, palladium-carbon, platinum oxide, platinumblack, Raney nickel, etc.).

When formic acid is used as the reducing agent, the reaction is usuallycarried out at a temperature of from room temperature to about 200° C.,peferably about 50° C. to about 150° C., for about 1 to 10 hours. Theformic acid is usually used in a large excess amount to the compound(7).

When a hydrogenating reducing agent is used, the reaction is usuallycarried out at a temperature of about -30° C. to about 100° C.,preferably about 0° C. to about 70° C., for about 30 minutes to about 12hours. The reducing agent is usually used in an amount of 1 to 20 moles,preferably 1 to 6 moles, to 1 mole of the compound (7). When lithiumaluminum hydride is used as the reducing agent, it is preferable to usea solvent selected from ethers (e.g. diethyl ether, dioxane,tetrahydrofuran, diglyme, etc.) and aromatic hydrocarbons (e.g. benzene,toluene, xylene, etc.).

When a catalytic reducing agent is used, the reaction is usually carriedout under atmospheric pressure to about 20 atm., preferably atmosphericpressure to about 10 atm. under hydrogen atmosphere or in the presenceof a hydrogen donor (e.g. formic acid, ammonium formate, cyclohexene,hydrazine hydrate, etc.) at a temperature of about -30° C. to about 100°C., preferably about 0° C. to about 60° C., for about 1 to 12 hours. Thecatalytic reducing agent is usually used in an amount of about 0.1 to40% by weight, preferably about 1 to 20% by weight, of the amount of thecompound (7). The compound (9) is usually used at least in equivalentamount, preferably equivalent to a large excess amount, to the compound(7). ##STR21## wherein R¹, R², R¹², R¹⁷, R¹⁸, X and W are as definedabove, and R^(11a) is a lower alkyl. ##STR22## wherein R¹, R², R¹¹, Xand W are as defined above, and R^(12a) is a cycloalkyl.

The reaction of the compound (10) and the compound (11) in the ReactionScheme-5A and the reaction of the compound (12) and the compound (13) inthe Reaction Scheme-5B are carried out in the same manner as in thereaction of the compound (7) and the compound (8) in the above ReactionScheme-4.

Besides, the reaction of the compound (10) and the compound (9) in theReaction Scheme-5A is carried out in the same manner as in the reactionof the compound (7) and the compound (9) in the above Reaction Scheme-4.##STR23## wherein R¹, R², R⁴, R¹⁶, R⁶, R⁷, X, W, and A are as definedabove, l is 0 or an integer of 1 to 3, l' and l" are each an integer of1 to 3, provided that l+l' and l+l' are each an integer not more than 3.##STR24## wherein R¹, R², R⁴, R¹⁶, X, W, A, l, l', and l" are as definedabove, and R¹⁹ is a lower alkanoyloxy, R²⁰ is a lower alkanoyloxy,hydroxy or phthalimido, R²¹ is the same as as R¹⁹ and R²⁰, and M is analkali metal (e.g. potassium, sodium, etc.).

The reaction of the compound (1g) and the compound (14) in the ReactionScheme-6A and the reaction of the compound (1g) and the compound (15) or(16) in the Reaction Scheme-6B can be carried out under the sameconditions as in the reaction of the compound (7) and the compound (8)in the above Reaction Scheme-4. In the reaction, an alkali metal halide(e.g. sodium iodide, potassium iodide, etc.) may be added to thereaction system. ##STR25## wherein R¹, R², R⁴, R¹⁶, W, l, l', l" and Aare as defined above.

The reaction of converting the compound (1j) into the compound (1k) canbe carried out by reacting the compound (1j) with hydrazine in anappropriate solvent or by hydrolyzing the compound (1j). The solventused in the reaction with hydrazine includes water and further the samesolvent as used in the reaction of the compound (2b) and the compound(4) in the above Reaction Scheme-2. The reaction is usually carried outat a temperature of from room temperature to about 120° C., preferablyabout 0° C. to about 100° C., for about 0.5 to 5 hours. Hydrazine isusually used in an amount of at least 1 mole, preferably about 1 to 5moles, to 1 mole of the compound (1j).

The hydrolysis can be carried out in an appropriate solvent or withoutsolvent in the presence of an acid or a basic compound. The solventincludes, for example, water, lower alcohols (e.g. methanol, ethanol,isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.),ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether,etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixtureof these solvents. The acid includes, for example, mineral acids (e.g.hydrochloric acid, sulfuric acid, hydrobromic acid, etc.) and organicacids (e.g. formic acid, acetic acid, aromatic sulfonic acids, etc.).The basic compound includes, for example, metal carbonates (e.g. sodiumcarbonate, potassium carbonate, etc.), metal hydroxides (e.g. sodiumhydroxide, potassium hydroxide, calcium hydroxide, etc.), and the like.The reaction is usually carried out at a temperature of from roomtemperature to about 200° C., preferably from room temperature to about150° C., for about 10 minutes to 25 hours. ##STR26## wherein R¹, R², R⁴,W, R¹⁶, l, l', l", X, and A are as defined above, and R²² is a loweralkanoyl.

The reaction of the compound (1l) and the compound (17) is carried outunder the same conditions as in the reaction of the compound (7) and thecompound (8) in the Reaction Scheme-4. In the reaction, an alkali metalhalide (e.g. sodium iodide, potassium iodide, etc.) may be added to thereaction system.

The reaction of converting the compound (1m) into the compound (1i) canbe carried out under the same condition as in the hydrolysis of thecompound (1j) in the Reaction Scheme-7. ##STR27## wherein R¹, R², R⁴, W,R¹⁶, l, l', l", and X are as defined above, and R²³ is a lower alkyl, alower alkanoyloxy-substituted lower alkyl, a halogen-substituted loweralkyl, a carboxy-substituted lower alkyl, a carbamoyl-substituted loweralkyl, a hydroxy-substituted lower alkyl, a loweralkoxycarbonyl-substituted lower alkyl, a phthalimido-substituted loweralkyl, an aminocarbonyl-lower alkyl having optionally a lower alkylsubstituent, or a group of the formula: ##STR28## (A, R⁶ and R⁷ are asdefined above).

The reaction of the compound (1n) and the compound (18) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. In the reaction, analkali metal halide (e.g. sodium iodide, potassium iodide, etc.) may beadded to the reaction system. ##STR29## wherein R¹, R², R⁴, W, R¹⁶, R¹⁷,R¹⁸, l, X, and A are as defined above, and R^(6') is hydrogen atom, alower alkyl having optionally a hydroxy substituent, a lower alkanoyl,or benzoyl, R^(7a) is a lower alkyl having optionally a hydroxysubstituent, and R^(7b) is a lower alkanoyl or benzoyl.

The reaction of the compound (1p) and the compound (19) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4.

The reaction of the compound (1p) and the compound (20) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the Reaction Scheme-1.

Besides, the compound (1r) can also be obtained by reacting the compound(1p) with a compound of the formula: (R^(7b))₂ O (R^(7b) is as definedabove). The reaction can be carried out in an appropriate solvent orwithout solvent in the presence or absence, peferably presence, of abasic compound. The solvent includes, for example, the above-mentionedaromatic hydrocarbons, lower alcohols (e.g. methanol, ethanol, propanol,etc.), dimethylformamide, dimethylsulfoxide, and further halogenatedhydrocarbons (e.g. chloroform, methylene chloride, etc.), acetone,pyridine, etc. The basic compound includes, for example, tertiary amines(e.g. triethylamine, pyridine, etc.), sodium hydroxide, potassiumhydroxide, sodium hydride, and the like. The above reaction can also becarried out in a solvent such as acetic acid or benzoic acid in thepresence of a mineral acid (e.g. sulfuric acid, etc.). The acidanhydride is usually used in an equimolar amount or more, preferably 1to 10 moles, to 1 mole of the starting compound, and the reaction isusually carried out at a temperature of about 0° C. to about 200° C.,preferably from about 0° C. to about 150° C., for about 0.5 to 15 hours.##STR30## wherein R¹, R², R⁴, R¹⁰, W, and B are as defined above.

The reaction of the compound (1s) and the compound (21) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. ##STR31## wherein R¹,R², R⁴, W, R⁹, R¹⁰, X, and B are as defined above.

The reaction of the compound (1u) and the compound (21) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. In the reaction, analkali metal halide (e.g. sodium iodide, potassium iodide, etc.) may beadded to the reaction system. ##STR32## wherein R¹, R², R⁴, W, and B areas defined above, and R²⁴ is a lower alkyl.

The reaction of the compound (2b) and the compound (22) can be carriedout in an appropriate inert solvent. The inert solvent includes, forexample, aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.),ethers (e.g. tetrahydrofuran, dioxane, diethylene glycol dimethyl ether,etc.), lower alcohols (e.g. methanol, ethanol, isopropanol, butanol,etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform,carbon tetrachloride, etc.), acetic acid, ethyl acetate, acetonitrile,dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, andthe like. The amount of the compound (2b) and the compound (22) is notcritical, but the compound (22) is usually used in an amount of at leastone mole, preferably 1 to 2 moles, to 1 mole of the compound (2b). Thereaction is usually carried out at a temperature of from about 0° C. toabout 150° C., preferably from about 0° C. to about 100° C., for about30 minutes to about 10 hours.

The esterification of the compound (1w) is usually carried out byreacting the starting compound with an alcohol (e.g. methanol, ethanol,isopropanol, etc.) in the presence of a mineral acid (e.g. hydrochloricacid, sulfuric acid, etc.) and a halogenating agent (e.g. thionylchloride, phosphorus oxychloride, phosphorus pentachloride, phosphorustrichloride, etc.) at a temperature of 0° C. to 150° C., preferably 50°C. to 100° C., for about 1 to 10 hours.

The hydrolysis of the compound (1x) can be carried out under the sameconditions as in the hydrolysis of the compound (1j) in the ReactionScheme-7. ##STR33## wherein R¹, R², R⁴, W, B, M, and X are as definedabove, and R²⁵ is a phenyl which has optionally 1 to 3 substituentsselected from a lower alkyl, a lower alkoxy and an amino havingoptionally a lower alkanoyl substituent, or naphthyl, and R^(25') is aphenoxy which has optionally 1 to 3 substituents selected from a loweralkyl, a lower alkoxy and an amino having optionally a lower alkanoylsubstituent, naphthyloxy or phthalimido.

The reaction of the compound (1u) and the compound (23) or (23a) can becarried out under the same conditions as in the reaction of the compound(7) and the compound (8) in the above Reaction Scheme-4.

The compound (1y) wherein R^(25') is phthalimido can be converted intothe compound (1y) wherein R^(25') is amino under the same conditions asin the reaction of converting the compound (1j) into the compound (1k)in the above ##STR34## wherein R¹, R² and R³ are as defined above, andR²⁶ is oxo, R²⁷ is hydroxy, and W' is the same as W, provided that thesubstituents on the group --(CH₂)_(p) -- or --CH═CH--(CH₂)_(q) -- are 0to 2, and R²⁸ and R²⁹ are the same or different and are each hydrogenatom, a lower alkenyl, a cycloalkyl, an oxiranyl-substituted loweralkyl, a lower alkyl having 1 to 2 substituents selected from a loweralkoxy, hydroxy and an amino having optionally a lower alkylsubstituent, a phenyl-lower alkyl, a pyridyl-lower alkyl, acyano-substituted lower alkyl, a lower alkoxycarbonyl-substituted loweralkyl, a carbamoyl-substituted lower alkyl, a carboxy-substituted loweralkyl, a tetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl which has optionallya phenyl-lower alkyl substituent, an aminocarbonyl-lower alkyl havingoptionally a lower alkyl substituent, or a lower alkyl, or R²⁸ and R²⁹may bind together with the nitrogen atom to which they bond to form a 5-or 6-membered saturated heterocyclic group with or without beingintervened with nitrogen or oxygen atom, which heterocyclic ring mayoptionally have a substituent selected from a lower alkyl, aphenyl-lower alkyl, or a lower alkanoyl.

The conversion of the compound (1A) into the compound (1B) is carriedout by reduction thereof. The reducing reaction is preferably carriedout by using a hydrogenating reducing agent (e.g. lithium aluminumhydride, sodium boro hydride, diborane, etc.). The reducing agent isusually used in an amount of at least one mole, preferably 1 to 15moles, to 1 mole of the starting compound. The reducing reaction isusually carried out in an appropriate solvent, for example, water,alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g.tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.), or amixture of these solvents, at a temperature of from about -60° C. toabout 150° C., peferably about -30° C. to about 100° C., for about 10minutes to 15 hours. When lithium aluminum hydride or diborane is usedas the reducing agent, it is preferable to use an anhydrous solvent suchas tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.

The reaction of converting the compound (1A) into the compound (1C) isusually carried out in an appropriate solvent or without solvent in thepresence or absence of a dehydrating agent. The solvent includes, forexample, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.),aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenatedhydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbontetrachloride, etc.), aprotic polar solents (e.g. dimethylformamide,dimethylacetamide, N-methylpyrrolidone, etc.), or a mixture of thesesolvents. The dehydrating agent includes, for example, conventionaldrying agent used for dehydrating solvents (e.g. molecular sieves,etc.), mineral acids (e.g. hydrochloric acid, sulfuric acid, boronetrifluoride, etc.), organic acids (e.g. p-toluenesulfonic acid, etc.),and the like. The reaction is usually carried out at a temperature offrom room temperature to about 250° C., preferably from about 50° C. toabout 200° C., for about 1 to 48 hours. The amount of the compound (24)is not critical, but it is usually used at least in an equivalentamount, preferably equimolar to largely excess to the amount of thecompound (1A). The dehydrating agent is preferably used in a largelyexcess amount in case of the drying agent and in a catalytic amount incase of the acid.

The subsequent reducing reaction can be carried out by various methods,for example by catalytically hydrogenating the compound in anappropriate solvent in the presence of a catalyst. The solvent includes,for example, water, acetic acid, alcohols (e.g. methanol, ethanol,isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.),ethers (e.g. diethylene glycol dimethyl ether, dioxane, tetrahydrofuran,diethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.),aprotic polar solvents (e.g. dimethylformamide, etc.), or a mixture ofthese solvents. The catalyst includes, for example, palladium, palladiumblack, palladium-carbon, platinum, platinum oxide, copper chromite,Raney nickel, and the like. The catalyst is usually used in an amount of0.02 to 1 part by weight to 1 part by weight of the starting compound.The reaction is usually carried out at a temperature of from about -20°C. to about 100° C., peferably about 0° C. to about 70° C., under ahydrogen atmospheric pressure of 1 to 10 atm. for about 0.5 to 20 hours.

Although the reducting reaction can be carried out under the aboveconditions, it is preferably carried out by using a hydrogenatingreducing agent. The hydrogenating reducing agent includes, for example,lithium aluminum hydride, sodium borohydride, diborane, etc., and it isusually used in an amount of at least one mole, preferably 1 to 10moles, to 1 mole of the compound (1A). The reaction is usually carriedout in an appropriate solvent, such as water, lower alcohols (e.g.methanol, ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran,diethyl ether, diglyme, etc.), dimethylformamide, or a mixture of thesesolvents, at a temperature of about -60° C. to about 50° C., preferablyabout -30° C. to room temperature, for about 10 minutes to about 5hours. When lithium aluminum hydride or diborane is used as the reducingagent, it is preferable to use an anhydrous solvent such as diethylether, tetrahydrofuran, diglyme, etc.

The compound (1C) wherein at least one of R²⁸ and R²⁹ is hydrogen atomcan be converted into the compound (1C) wherein at least one of R²⁸ andR²⁹ is a lower alkyl by reacting the compound (1C) with the compound (8)or the compound (9) under the same conditions as in the reaction of thecompound (7) and the compound (8) or (9) in the above Reaction Scheme-4.##STR35## wherein R¹, R², R³, R¹⁴, R¹⁵, W', and M are as defined above,and R³¹ is a phenyl-lower alkyl, and R³⁰ is a lower alkoxycarbonyl.

The reaction of converting the compound (1D) into the compound (1E) canbe carried out under the same conditions as in the reaction ofconverting the compound (1A) into the compound (1B) in the aboveReaction Scheme-15.

The reaction of converting the compound (1D) into the compound (1F) canbe carried out under the same conditions as in the hydrolysis reactionof the compound (1j) in the above Reaction Scheme-7.

The reaction of the compound (1F) and the compound (25) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The halogenation of the compound (1F) can be carried out under aconventional condition for halogenation of a carboxylic acid. Thereaction of the thus-obtained carboxylic acid halide of the compound(1F) with the compound (26) is carried out in an appropriate solvent inthe presence or absence of a basic compound. The solvent includes, forexample, halogenated hydrocarbons (e.g. methylene chloride, chloroform,etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.),ethers (e.g. diethyl ether, tetrahydrofuran, dimethoxyethane, etc.),esters (e.g. methyl acetate, ethyl acetate, etc.), aprotic polarsolvents (e.g. N,N-dimethylformamide, dimethylsulfoxide,hexamethylphosphoric triamide, etc.), alcohols (e.g. methanol, ethanol,propanol, butanol, 3-methoxy-1-butanol, ethyl cellosolve, methylcellosolve, etc.), pyridine, acetone, acetonitrile, water, or a mixtureof these solvents. The basic compound includes, for example, organicbases such as triethylamine, trimethylamine, pyridine, dimethylaniline,N-methylmorpholine, DBN, DBU, DABCO, etc., inorganic bases such aspotassium carbonate, sodium carbonate, potassium hydroxide, sodiumhydroxide, potassium hydride, sodium hydride, silver carbonate,alcoholates (e.g. sodium methylate, sodium ethylate, etc.), and thelike. The compound (26) is usually used in an amount of at least 1 mole,preferably 1 to 1.5 mole, to 1 mole of the carboxylic acid halide of thecompound (1F). The reaction is usually carried out at a temperature offrom -30° C. to about 180° C., preferably from about 0° C. to about 150°C., for about 5 minutes to 30 hours.

The reaction of the compound (1H) and the compound (27) is carried outin an appropriate solvent or without solvent at a temperature of fromabout 0° C. to about 200° C., preferably from room temperature to about150° C. The solvent includes the same solvents as used in the abovereaction of the carboxylic acid halide of the compound (1F) and thecompound (26). The compound (27) is preferably used in an amount largelyexcess to the the compound (1H). The reaction is usually completed in areaction time of about 1 to 5 hours.

The reaction of converting the compound (1I) into the compound (1J) canbe carried out by reducing the compound. The reducing reaction isusually carried out by catalytically hydrogenating the compound in anappropriate solvent in the presence of a catalyst. The solvent includes,for example, water, acetic acid, alcohols (e.g. methanol, ethanol,isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.),ethers (e.g. dioxane, tetra-hydrofuran, diethyl ether, diethylene glycoldimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate,etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, etc.), aceticacid, or a mixture of these solvents. The catalyst includes, forexample, palladium, palladium black, palladium-carbon, platinum,platinum oxide, copper chromite, Raney nickel, and the like. Thecatalyst is usually used in an amount of 0.02 to 1 part by weight to 1part by weight of the starting compound. The reaction is usually carriedout at a temperature of from about -20° C. to about 100° C., peferablyabout 0° C. to about 80° C., under a hydrogen atmospheric pressure of 1to 10 atm. for about 0.5 to 20 hours. ##STR36## wherein R¹, R², R³, W',l, R¹⁷, R¹⁸, and X are as defined above, and R¹⁴ a is hydrogen atom, alower alkyl, a lower alkanoyl, a lower alkenyl, a cycloalkyl, anoxiranyl-substituted lower alkyl, a lower alkyl having 1 to 2substituents selected from a lower alkoxy, hydroxy and an amino havingoptionally a lower alkyl substituent, a phenyl-lower alkyl, apyridyl-lower alkyl, a lower alkylsulfonyl, benzoyl, a loweralkoxycarbonyl, anilinocarbonyl, an aminocarbonyl having optionally alower alkyl substituent, a cyano-substituted lower alkyl, a loweralkoxycarbonyl-substituted lower alkyl, a carbamoyl-substituted loweralkyl, a carboxy-substituted lower alkyl, atetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent, a halogen-substituted lower alkanoyl, animiazolyl-substituted lower alkanoyl, an amino-lower alkanoyl havingoptionally a substituent selected from a lower alkyl and a loweralkoxycarbonyl, an aminocarbonyl-lower alkyl having optionally a loweralkyl substituent, or a phenyl-lower alkoxycarbonyl, R^(15a) is a loweralkyl, a cycloalkyl, an oxiranyl-substituted lower alkyl, a lower alkylhaving 1 to 2 substituents selected from a lower alkoxy, hydroxy and anamino having optionally a lower alkyl substituent, a phenyl-lower alkyl,a pyridyl-lower alkyl, a lower alkylsulfonyl, a cyano-substituted loweralkyl, a lower alkoxycarbonyl-substituted lower alkyl, acarbamoyl-substituted lower alkyl, a carboxy-substituted lower alkyl, atetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent, an aminocarbonyl-lower alkyl havingoptionally a lower alkyl substituent, or a lower alkenyl, and R^(15b) isa lower alkanoyl, a phenyl-lower alkoxycarbonyl, benzoyl, a loweralkoxycarbonyl, a halogen-substituted lower alkanoyl, animidazolyl-substituted lower alkanoyl, or an amino-lower alkanoyl havingoptionally a substituent selected from a lower alkyl and a loweralkoxycarbonyl.

The reaction of the compound (1K) and the compound (28) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4.

The reaction of the compound (1K) and the compound (29) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-l. The compound (1M) canalso be obtained by reacting the compound (1K) with a compound of theformula (R^(15b))₂ O (wherein R^(15b) is as defined above). The reactioncan be carried out under the same conditions as in the reaction of thecompound (1p) and the compound of the formula: (R^(7b))₂ O as describedhereinbefore.

The compound (1M) wherein R^(15b) is formyl can also be prepared byreacting the compound (1K) with a formate of the formula: HCOOR⁸² (R⁸²is a lower alkyl). The reaction is usually carried out in the solvent asused in the reaction of the compound (7) and the compound (8) in theabove Reaction Scheme-4 or without solvent, at a temperature of about 0°C. to about 200° C., preferably about 0° C. to about 170° C., for about30 minutes to about 30 hours. The formate is preferably used in alargely excess amount to the compound (1K). ##STR37## wherein R¹, R²,R⁴, R¹⁶, W, l, l' and l" are as defined above, and R³² is a loweralkoxycarbonyl-substituted lower alkoxy, R³³ is a carbamoyl-substitutedlower alkoxy, R³⁴ is a carboxy-substituted lower alkoxy, R⁴⁴ is an aminohaving optionally a lower alkyl substituent, and R⁴⁵ is anaminocarbonyl-lower alkoxy having optionally a lower alkyl substituent.

The conversion of the compound (1N) into the compound (10) can becarried out by reacting the compound with aqueous ammonia in anappropriate solvent in an autoclave. The solvent includes the samesolvents as used in the reaction of the carboxylic acid halide and theamine (2) in the above Reaction Scheme-1. The aqueous ammonia is used ina largely excess amount to the compound (1N). The reaction proceedsadvantageously by adding an ammonium halide (e.g. ammonium chloride,etc.) to the reaction system. The reaction is usually carried out at atemperature of from room temperature to about 200° C., preferably fromroom temperature to about 150° C., for about 1 to 10 hours.

The reaction of converting the compound (1N) into the compound (1P) canbe carried out under the same conditions as in the hydrolysis of thecompound (1j) in the above Reaction Scheme-7.

The reaction of the compound (1P) and the compound (30) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. ##STR38## wherein R¹,R², R⁴, R¹⁶, W, l, l' and l" are as defined above.

The reducing reaction in the above reaction scheme is usually carriedout, for example, (i) with a reducing catalyst in an appropriate solventor (ii) with a reducing agent such as a mixture of a metal or metal saltwith an acid, or a mixture of a metal or metal salt with an alkali metalhydroxide, a sulfide or an ammonium salt in an appropriate inertsolvent.

In case of using a reducing catalyst, the solvent includes, for example,water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol,etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g.dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethylether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aproticpolar solvents (e.g. N,N-dimethylformamide, etc.), or a mixture of thesesolvents. The catalyst includes, for example, palladium, palladiumblack, palladium-carbon, platinum, platinum oxide, copper chromite,Raney nickel, and the like. The catalyst is usually used in an amount of0.02 to 1 part by weight to 1 part by weight of the starting compound.The reaction is usually carried out at a temperature of from about -20°C. to about 150° C., peferably about 0° C. to about 100° C., under ahydrogen pressure of 1 to 10 atm. for about 0.5 to 10 hours. In thereaction, an acid such as hydrochloric acid may optionally added to thereaction system.

In case of the above method (ii), the reducting agent includes a mixtureof iron, zinc, tin or stannous chloride and a mineral acid (e.g.hydrochloric acid, sulfuric acid, etc.), or a mixture of iron, ferroussulfate, zinc or tin and an alkali metal hydroxide (e.g. sodiumhydroxide., etc.), a sulfide (e.g. ammonium sulfide, etc.), aqueousammonia, or an ammonium salt (e.g. ammonium chloride, etc.). The inertsolvent includes, for example water, acetic acid, methanol, ethanol,dioxane, and the like. The reducing reaction conditions are determineddepending on the kinds of the reducting agent, but in case of using areducing agent comprising stannous chloride and hydrochloric acid, forexample, it is preferably carried out at a temperature of about 0° C. toroom temperature for about 0.5 to 10 hours. The reducing agent isusually used in an amount of at least one mole, preferably 1 to 5 moles,to 1 mole of the starting compound. ##STR39## wherein R¹, R², R⁴, R¹⁶,R¹⁷, R¹⁸, l, l', l" and W are as defined above, and R³⁶ is a loweralkyl, R³⁷ is a lower alkanoyl, and R³⁵ is hydrogen atom, a lower alkylor a lower alkanoyl.

The reaction of the compound (1S) and the compound (31) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4.

The reaction of the compound (1S) and the compound (32) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. Besides, the compound(1U) can also be obtained by reacting the compound (1S) with a compoundof the formula: (R³⁷)₂ O (R³⁷ is as defined above). The reaction iscarried out under the same conditions as in the above reaction of thecompound (1p) and a compound of the formula: (R^(7b))₂ O.

The compound (1) wherein R⁸ is a phenyl-lower alkoxycarbonyl can beconverted into the compound (1) wherein R⁸ is hydrogen atom in the samemanner as in the reaction of converting the compound (1I) into thecompound (1J) in the above Reaction Scheme-16.

Other derivatives of the starting compound (2) can be prepared, forexample, by the process as shown in the following reaction scheme.##STR40## wherein R¹, R², and W are as defined above.

The reaction of the compound (2) and the compound (33) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of converting the compound (34) into the compound (2a) canbe carried out under the same conditions as in the reducing reaction inthe above Reaction Scheme-19.

The starting compound (5) can be prepared, for example, by the processof the following reaction scheme. ##STR41## wherein R¹, R², and W are asdefined above, and R³⁸ is a lower alkyl.

The reaction of the compound (2) and the compound (35) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of converting the compound (36) into the compound (5) canbe carried out under the same conditions as in the hydrolysis reactionin the above Reaction Scheme-7. ##STR42## wherein R¹, R², R⁴, R¹⁶, l,l', l", X, and W are as defined above, and R³⁹ is a lower alkanoyl.

The reaction of the compound (1W) and the compound (37) can be carriedout under the same conditions as in the reaction of the compound (1n)and the compound (18) in the above Reaction Scheme-9.

The hydrolysis reaction of the compound (1X) can be carried out underthe same conditions as in the hydrolysis of the compound (1j) in theabove Reaction Scheme-7. ##STR43## wherein R¹, R², R⁴, R¹⁶, l, l', l",and W are as defined above, R⁴⁰ is a lower alkanoyl, and R⁴¹ is ahydroxy-substituted lower alkyl.

The reaction of converting the compound (1Y) into the compound (1Z) canbe carried out under the same conditions as in the reaction ofconverting the compound (1A) into the compound (1B) in the aboveReaction Scheme-15. ##STR44## wherein R¹, R², R⁴, R¹⁶, l, l', l", and Ware as defined above, R⁴² is a lower alkoxycarbonyl and R⁴³ is carboxyl.

The reaction of converting the compound (1aa) into the compound (1bb)can be carried out under the same conditions as in the hydrolysis of thecompound (1j) in the above Reaction Scheme-7.

The esterification reaction of the compound (1bb) can be carried outunder the same conditions as in the esterification of the compound (1w)in the above Reaction Scheme-13. ##STR45## wherein R¹, R², R⁴, and W areas defined above, and R⁴⁶ is a phenyl having optionally a lower alkylsubstituent.

The reaction of the compound (2b) and the compound (38) is usuallycarried out in an appropriate solvent or without solvent in the presenceor absence, preferably in the absence, of a basic compound. The solventand basic compound are the same as those used in the reaction of thecarboxylic acid halide and the amine (2) in the above Reaction Scheme-1.

The compound (38) is usually used in an amount of about 1 to 5 moles,preferably about 1 to 3 moles, to 1 mole of the compound (2b). Thereaction is usually carried out at a temperature of from about 0° C. toabout 200° C., preferably from room temperature to about 150° C., forabout 5 minutes to about 30 hours. In the reaction, a boron compound(e.g. boron trifluoride etherate, etc.) may be added to the reactionsystem. ##STR46## wherein R¹, R², R⁴, W, and X are as defined above, andR⁴⁷ is a phenylsulfonyl which has optionally a substituent selected froma halogen atom and a lower alkyl on the phenyl ring, orquinolylsulfonyl.

The reaction of the compound (2b) and the compound (39) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. ##STR47## wherein R¹,R², R⁴, W, R¹⁷, R¹⁸, and X are as defined above, R⁴⁸ is a phenyl-loweralkoxycarbonyl, a lower alkanoyl, an amino-lower alkanoyl havingoptionally a lower alkyl substituent, and R⁴⁹ is a lower alkyl or acarbamoyl-lower alkyl.

The reaction of the compound (1ee) and the compound (40) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of the compound (1ee) and the compound (41) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4, provided that in the reaction product (1ff) producedby the reaction of the compound (1ee) and the compound (9), the groupR⁴⁹ is a lower alkyl. ##STR48## wherein R¹, R², R⁵, and W are as definedabove, and R⁵⁰ is a benzoyl having optionally a halogen substituent onthe phenyl ring.

The reaction of the compound (7) and the compound (42) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. ##STR49## wherein R¹,W', R²⁶, R², and R³ are as defined above, R¹⁰³ is hydroxy or sulfoxy,and R⁵¹ is hydroxyimino or sulfoxyimino.

The reaction of the compound (1A) and the compound (43) is usuallycarried out in an appropriate inert solvent in the presence or absenceof a basic compound. The basic compound includes, for example, inorganicbasic compounds such as sodium hydroxide, potassium hydroxide, sodiumcarbonate, potassium carbonate, etc., and organic basic compounds suchas piperidine, pyridine, triethylamine, 1,5-diazabicyclo[4.3.0]nonene-5(DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU),1,4-diazabicyclo[2.2.2]octane (DABCO), etc. The inert solvent includes,for example, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.),ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, ethylene glycolmonomethyl ether, etc.), aromatic hydrocarbons (e.g. benzene, toluene,xylene, etc.), halogenated hydrocarbons (e.g. dichloromethane,dichloroethane, chloroform, carbon tetrachloride, etc.), pyridine,dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide,etc., or a mixture of these solvents. The compound (43) is usually usedat least in equivalent amount, preferably 1 to 5 moles, to 1 mole of thecompound (1A). The reaction is usually carried out at a temperature offrom room temperature to about 200° C., preferably from about 50° C. to150° C., for about 1 to 10 hours. ##STR50## wherein R¹, W', R²⁷, R², M,and R³ are as defined above, and R⁵² is a halogen atom.

The halogenation of the compound (1B) is usually carried out in anappropriate solvent or without solvent by reacting the compound (1B)with a halogenating agent.

The halogenating agent includes mineral acids (e.g. hydrochloric acid,hydrobromic acid, etc.), N,N-diethyl-1,2,2-trichlorovinylamide,phosphorus pentachloride, phosphorus pentabromide, phosphorusoxychloride, thionyl chloride, methanesulfonyl chloride, or acombination of a phenyl-lower alkyl halide (e.g. p-toluenesulfonylchloride, etc.) and a basic compound. The basic compound includes thesame compounds as used in the reaction of the compound (1A) and thecompound (43) in the above Reaction Scheme-30. The solvent includes, forexample, ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenatedhydrocarbons (e.g. chloroform, methylene chloride, carbon tetrachloride,etc.), and the like. The amount of the halogenating agent may varydepending on the kinds of the halogenating agents, and in case of acombination of a phenyl-lower alkyl halide (e.g. p-toluenesulfonylchloride, etc.) and a basic compound, it is used in an amount of atleast 1 mole, preferably 1 to 2 moles, to 1 mole of the compound (1B),and in case of other halogenating agents, it is used at least in anequimolar amount, usually in a largely excess amount, to the compound(1B). The reaction is usually carried out at a temperature of from roomtemperature to about 150° C., preferably from room temperature to about80° C., for about 1 to 80 hours.

The reaction of the compound (1jj) and the compound (44) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reducing reaction of the compound (1kk) can be carried out under thesame conditions as in the reducing reaction using a reducing catalystfor converting the compound (1A) into the compound (1C) in the aboveReaction Scheme-15. ##STR51## wherein R¹, W', R², R³, R²⁷, X, and A areas defined above, R⁵³ is a lower alkanoyloxy having optionally a halogensubstituent, R⁵⁴ is a lower alkoxy, an amino-lower alkanoyloxy havingoptionally a lower alkyl substituent, or a group of the formula:##STR52## (A, R⁸² and R⁸³ are as defined above), R⁵⁵ is a loweralkoxycarbonyl-substituted lower alkoxy, R⁵⁶ is a carboxy-substitutedlower alkoxy, R⁵⁷ is an aminocarbonyl-lower alkoxy having optionally alower alkyl substituent, R^(54a) is a lower alkyl, an amino-loweralkanoyl having optionally a lower alkyl substituent, or a group of theformula: ##STR53## (A, R⁸² and R83 are as defined above), R^(55a) is alower alkoxycarbonyl-substituted lower alkyl, R⁵⁸ and R⁵⁹ are the sameor different and are each hydrogen atom or a lower alkyl, and R^(22a) isa lower alkanoyl having optionally a halogen substituent. ##STR54##wherein R¹, W', R², R³, X, R²⁷, and A are as defined above, and R⁶¹ andR⁶² are the same or different and are each hydrogen atom, a lower alkylor a lower alkanoyl.

The reaction of the compound (1B) and the compound (45) or the compound(46) in the Reaction Scheme-32A can be carried out under the sameconditions as in the reaction of the compound (1n) and the compound (18)in the above Reaction Scheme-9.

The reaction of the compound (1B) and the compound (47) and the reactionof the compound (1B) and the compound (48) can be carried out under thesame conditions as in the reaction of the compound (1n) and the compound(18) in the above Reaction Scheme-9.

The reaction of converting the compound (1oo) into the compound (1pp)can be carried out under the same conditions as in the hydrolysisreaction of the compound (1j) in the above Reaction Scheme-7.

The reaction of the compound (1oo) and the compound (49) and thereaction of the compound (1pp) and the compound (49) can be carried outunder the same conditions as in the reaction of the compound (2) and thecompound (3) in the above Reaction Scheme-1.

The reaction of the compound (1B) and the compound (49a) in the ReactionScheme-32B can be carried out under the same conditions as in thereaction of the compound (1n) and the compound (18) in the aboveReaction Scheme-9. ##STR55## wherein R¹, W', R², R³, R²⁷, R⁶¹, R⁶², M,and X are as defined above, R⁶⁰ is a halogen-substituted lower alkyl,R⁶⁴ is a phthalimido-substituted lower alkyl, R⁶³ is an amino-loweralkoxy having optionally a substituent selected from a lower alkyl and alower alkanoyl, or a phthalimido-substituted lower alkoxy, and R⁶⁵ is anamino-substituted lower alkyl.

The reaction of the compound (1B) and the compound (50) and the reactionof the compound (1B) and the compound (52) can be carried out under thesame conditions as in the reaction of the compound (1n) and the compound(18) in the above Reaction Scheme-9.

The reaction of the compound (1rr) and the compound (51) or the compound(23a) can be carried out under the same conditions as in the reaction ofthe compound (1g) and the compound (14) in the above Reaction Scheme-6.

The reaction of converting the compound (1tt) into the compound (1uu)can be carried out under the same conditions as in the reaction ofconverting the compound (1j) into the compound (1k) in the aboveReaction Scheme-7. ##STR56## wherein R¹, R², R³, R⁶¹, W', A, R¹⁷, R¹⁸,and X are as defined above, R^(62a) is a lower alkyl, and R^(62b) is alower alkanoyl.

The reaction of the compound (1vv) and the compound (53) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4.

The reaction of the compound (1vv) and the compound (54) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of the compound (1vv) and the compound (55) can be carriedout under the same conditions as in the reaction of the compound (1p)and the compound of the formula: (R^(7b))₂ O in the above ReactionScheme-10. ##STR57## wherein R¹, R², R³, and W' are as defined above,R^(58') and R^(59') are the same or different and are each hydrogenatom, a lower alkyl, or a lower alkanoyl.

The reaction of converting the compound (1yy) into the compound (1zz) isusually carried out by reducing the compound (1yy).

The reducting reaction is preferably carried out by using ahydrogenating reducing agent. The hydrogenating reducing agent includes,for example, lithium aluminum hydride, sodium boro hydride, diborane,etc. The reducing agent is usually used in an amount of at least onemole, preferably 1 to 15 moles, to 1 mole of the starting compound. Thereducing reaction is usually carried out in an appropriate solvent, suchas water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.),ethers (e.g. tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme,etc.), or a mixture of these soslvents, at a temperature of about -60°C. to about 150° C., preferably about -30° C. to 100° C., for about 10minutes to about 5 hours. When lithium aluminum hydride or diborane isused as the reducing agent, it is preferable to use an anhydrous solventsuch as diethyl ether, tetrahydrofuran, diglyme, etc. ##STR58## whereinR¹, W', R², R³, R^(62a), R^(62b), X, R¹⁷, R¹⁸, and A are as definedabove, R^(58a) is hydrogen atom, a lower alkyl or a lower alkanoyl.

The reaction of the compound (1AA) and the compound (53) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4.

The reaction of the compound (1AA) and the compound (54) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of the compound (1AA) and the compound (55) can be carriedout under the same conditions as in the reaction of the compound (1p)and the compound of the formula: (R^(7b))₂ O in the above ReactionScheme-10.

The compound (1BB) wherein R^(62b) is formyl can also be prepared byreacting the compound (1AA) with a formate of the formula: HCOOR⁸² underthe same conditions as in the reaction of the compound (1K) and thecompound of the formula: HCOOR⁸² as described hereinbefore.

The compounds of the formula (1) wherein W is sulfur atom or sulfinyl,or R⁸² and R⁸³ bind together with the nitrogen atom to which they bondto form thiomorpholino or 1-oxo-thiomorpholino can be converted into thecorresponding compounds of the formula (1) wherein W is sulfinyl orsulfonyl, or R⁸² and R⁸³ bind together with the nitrogen atom to whichthey bond to form 1-oxo-thiomorpholino or 1,1-dioxo-thiomorpholino,respectively, by oxidation thereof.

The oxidation reaction is carried out in an appropriate solvent in thepresence of an oxidizing agent. The solvent includes, for example,water, organic acids (e.g. formic acid, acetic acid, trifluoroaceticacid, etc.), alcohols (e.g. methanol, ethanol, etc.), halogenatedhydrocarbons (e.g. chloroform, dichloromethane, etc.), or a mixture ofthese solvents. The oxidizing agent includes, for example, peracids(e.g. performic acid, peracetic acid, trifluoro-peracetic acid,perbenzoic acid, m-chloroperbenzoic acid, o-carboxy-perbenzoic acid,etc.), hydrogen peroxide, sodium metaperiodate, dichromic acid,dichromates (e.g. sodium dichromate, potassium dichromate, etc.),permanganic acid, permanganates (e.g. potassium permanganate, sodiumpermanganate, etc.), lead salts (e.g. lead tetraacetate, etc.), and thelike. The oxidizing agent is usually used in an amount of at least 1mole, preferably 1 to 2 moles, to 1 mole of the starting compound.Besides, in cases of the oxidation of converting the sulfur atom intosulfonyl group, the oxidizing agent is usually used at least 2 moles,preferably 2 to 4 moles, to 1 mole of the starting compound. The abovereaction is usually carried out at a temperature of about -10° C. toabout 40° C., preferably from about -10° C. to room temperature, forabout 1 to 100 hours.

The compound (1) wherein R¹⁶ or R² is a lower alkoxy can be convertedinto the correspond compound (1) wherein R¹⁶ or R² is hydroxy by heatingthe compound in a mixture of an acid (e.g. hydrobromic acid,hydrochloric acid, etc.) and a solvent (e.g. water, methanol, ethanol,isopropyl alcohol, etc.) at 30 to 150° C., preferably at 50 to 120° C.

Besides, the compound (1) wherein R¹⁶ or R² is hydroxy can also beprepared by hydrolysis of the above compound (1) wherein R¹⁶ or R² is alower alkoxy. The hydrolysis can be carried out in an appropriatesolvent in the presence of an acid. The solvent includes, for example,water, lower alcohols (e.g. methanol, ethanol, isopropyl alcohol, etc.),ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons(e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), polarsolvents (e.g. acetonitrile, etc.), or a mixture of these solvents. Theacid includes, for example, mineral acids (e.g. hydrochloric acid,hydrobromic acid, etc.), Lewis acids (e.g. boron trifluoride, aluminumchloride, boron tribromide, etc.), iodides (e.g. sodium iodide,potassium iodide, etc.), or a mixture of the above Lewis acid andiodide. The reaction is usually carried out at a temperature of fromroom temperature to about 150° C., preferably from room temperature toabout 100° C., for about 0.5 to 30 hours. ##STR59## wherein R¹, R², R³,R⁶² b, and W' are as defined above, R^(51a) is hydroxyamino, and R⁶⁶ isa lower alkanoyloxyimino.

The reaction of the compound (1ii') and the compound (54) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of the compound (1ii') and the compound (55) can be carriedout under the same conditions as in the reaction of the compound (1p)and the compound of the formula:(R^(7b))₂ O in the above ReactionScheme-10. ##STR60## wherein R¹, R², R³, W', R²⁶, R¹⁴, R¹⁵, R^(62b), Xand M are as defined above, R⁶⁷ is methylidene, R⁶⁸ is a group of theformula: ##STR61## and R⁶⁹ is a group of the formula: ##STR62## (R¹⁴ andR¹⁵ are as defined above), or ##STR63## (R⁷ D is an amino havingoptionally a substituent selected from a lower alkyl and a loweralkanoyl, R⁷⁰ is a lower alkylsulfonyl, and W" is the same as the aboveW, provided that the number of the substituent in the groups --(CH₂)_(p)-- and --CH═CH--(CH₂)_(q) -- is 0 or 1.

The reaction of converting the compound (1A) into the compound (1EE) iscarried out in an appropriate solvent in the presence of a Wittigreagent and a basic compound. The Wittig reagent includes, for example,a phosphoric compound of the formula:

    [(R.sup.71).sub.3 P.sup.+ --CH.sub.2 --R.sup.72 ]X.sup.-   (A)

wherein R⁷¹ is phenyl, R⁷² is hydrogen atom or a lower alkyl, and X is ahalogen atom. The basic compound includes inorganic bases (e.g. metallicsodium, metallic potassium, sodium hydride, sodium amide, sodiumhydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,sodium hydrogen carbonate, etc.), metal alcoholates (e.g. sodiummethylate, sodium ethylate, potassium t-butoxide, etc.), alkyl or aryllithiums or lithium amides (e.g. methyl lithium, n-butyl lithium, phenyllithium, lithium diisopropylamide, etc.), organic bases (e.g. pyridine,piperidine, quinoline, triethylamine, N,N-dimethylaniline, etc.). Thesolvent includes any solvent which does not affect on the reaction, forexample, ethers (e.g. diethyl ether, dioxane, tetrahydrofuran,monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene,xylene, etc.), aliphatic hydrocarbons (e.g. n-hexane, heptane,cyclohexane, etc.), amines (e.g. pyridine, N,N-dimethylaniline, etc.),aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide,hexamethylphosphoric triamide, etc.), alcohols (e.g. methanol, ethanol,isopropanol, etc.), and the like. The reaction is usually carried out ata temperature of about -80° C. to about 150° C., preferably about -80°C. to about 120° C., for about 0.5 to 15 hours.

The reaction of converting the compound (1EE) into the compound (1LL)can be carried out under the same conditions as in the catalyticallyhydrogenation reaction for converting the compound (1A) into thecompound (1C) in the above Reaction Scheme-15.

The reaction of converting the compound (1EE) into the compound (1FF) iscarried out under the same conditions as in the reaction of convertingthe compound (1) wherein W is sulfur atom or sulfinyl into thecorresponding compound (1) wherein W is sulfinyl or sulfonylrespectively as described herebefore.

The reaction of the compound (1FF) and the compound (25) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reaction of converting the compound (1EE) into the compound (1E) canbe carried out by firstly subjecting it to hydroboration reaction andthen to oxidation.

The hydroboration reaction is carried out in a solvent such as ethers(e.g. diethyl ether, tetrahydrofuran, dioxane, etc.) in the presence ofa hydroborating agent at a temperature of from about 0° C. to about 50°C., preferaly about 0° C. to room temperature, for about 1 to 10 hours.The hydroborating agent includes boron hydride compounds, for example,BH₃.tetrahydrofuran, BH₃.S(CH₃)₂, BH₂ Cl, (CH₃)₂ CHC(CH₃)₂ BH₂, (CH₃)₂CHCH(CH₃)BH, ##STR64## and the like.

The subsequent oxidation is carried out in water in the presence of anoxidizing agent. The oxidizing agent includes, for example, alkalinehydrogen peroxides (e.g. hydrogen peroxide-sodium hydroxide, etc.), andair oxidation is also used. The reaction is usually carried out at atemperature of from room temperature to about 150° C., preferably fromroom temperature to about 100° C., for 0.5 to 7 hours.

The hydroborating agent and the oxidizing agent are each used in anamount of at least 1 mole, preferably 1 to 2 mole, to 1 mole of thecompound (1EE).

The reaction of the compound (1E) and the compound (54) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of the compound (1E) and the compound (55) can be carriedout under the same conditions as in the reaction of the compound (1p)and the compound of the formula: (R^(7b))₂ O in the above ReactionScheme-10.

The reaction of the compound (1E) and the compound (56) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reaction of the compound (1HH) and the compound (44) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reducing reaction of the compound (1JJ) can be carried out under thesame conditions as in the catalytic hydrogenation reaction forconverting the compound (1A) into the compound (1C) in the aboveReaction Scheme-15.

The reaction of converting the compound (1EE) into the compound (1MM)can be carried out by reacting with an oxidizing agent in an appropriatesolvent in the presence of a co-oxidizing agent.

The solvent used for the reaction with an oxidizing agent includes, forexample, pyridine, ethers (e.g. dioxane, tetrahydrofuran, diethyl ether,etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.),halogenated hydrocarbons (e.g. dichloromethane, dichloroethane,chloroform, carbon tetrachloride, etc.), esters (e.g. ethyl acetate,etc.), water, alcohols (e.g. methanol, ethanol, isopropanol, t-butanole,etc.), or a mixture of these solvents. The co-oxidizing agent includes,for example, organic amine N-oxides (e.g. pyridine N-oxide,N-ethyldiisopropylamine N-oxide, N-methylmorpholine N-oxide,trimethylamine N-oxide, triethylamine N-oxide, etc.). The oxidizingagent includes, for example, osmium tetraoxide, and the like. Theoxidizing agent is usually used in an amount of at least 1 mole,preferably 1 to 5 moles, to 1 mole of the starting compound. Thereaction is usually carried out at a temperature of from -20° C. to 150°C., preferably from room temperature to 100° C., for about 1 to 10hours. ##STR65## wherein R¹, R², R³, R²⁷, W', M, and X are as definedabove, R⁷³ is an aminocarbonyl having optionally a lower alkylsubstituent, R⁷⁴ is an aminocarbonyloxy having optionally a lower alkylsubstituent, R^(74') is a lower alkyl.

The reaction of the compound (1A) and the compound (57) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reaction of the compound (1A) and the compound (59) is carried outin an appropriate solvent in the presence of an acid. The solventincludes the same solvent as used in the reaction of the compound (7)and the compound (8) in the above Reaction Scheme-4. The acid includes,for example, mineral acids (e.g. hydrochloride acid, sulfuric acid,etc.), sulfonic acids (e.g. methanesulfonic acid, p-toluenesulfonicacid, etc.), alkanoic acids (e.g. trifluoroacetic acid, etc.), and thelike. The compound (59) is used in an amount of at least 1 mole,preferably 1 to 5 moles, to 1 mole of the compound (1A). The reaction isusually carried out at a temperature of from room temperature to about150° C., preferably from room temperature to about 100° C., for about 1to 7 hours.

The reaction of the compound (1A) and the compound (58) can be carriedout under the same conditions as in the reaction of the compound (2b)and the compound (38) in the above Reaction Scheme-26. ##STR66## whereinR¹, R², R³, X, and q are as defined above, and R⁷⁵, R⁷⁶ and R⁷⁷ are eacha lower alkyl, and the carbon atom in the formula: --(CH₂)_(q) -- may besubstituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, or a groupof the formula: ##STR67## (R¹³ is as defined above), and further thegroup: --(CH₂)_(q) -- may optionally have 1 to 3 substituents selectedfrom a lower alkyl having optionally a hydroxy substituent, a loweralkoxycarbonyl, carboxyl, hydroxy, oxo, a lower alkanoyloxy havingoptionally a halogen substituent, an amino-lower alkyl having optionallya substituent selected from a lower alkyl and a lower alkanoyl, a loweralkanoyloxy-substituted lower alkyl, a lower alkylsulfonyloxy-loweralkyl, an azido-lower alkyl, a group of the formula: ##STR68## anaminocarbonyloxy having optionally a lower alkyl substituent, a loweralkoxy, a lower alkoxycarbonyl-substituted lower alkoxy, acarboxy-substituted lower alkoxy, an aminocarbonyl-lower alkoxy havingoptionally a lower alkyl substituent, an amino-lower alkoxy havingoptionally a substituent selected from a lower alkyl and a loweralkanoyl, a phthalimido-substituted lower alkoxy, hydroxyimino, a loweralkanoyloxyimino, a lower alkylidene, a halogen atom, azido,sulfoxyimino, a group of the formula: ##STR69## (R⁸¹ is hydrogen atom ora lower alkyl), hydrazino, pyrrolyl, an amino-lower alkanoyloxy havingoptionally a lower alkyl substituent, a group of the formula: ##STR70##(A is as defined above, and R⁸² and R⁸³ are the same or different andare each hydrogen atom, a lower alkyl, a carbamoyl-substituted loweralkyl, a hydroxy-substituted lower alkyl, or a pyridyl-lower alkyl, orR⁸² and R⁸³ may bind together with nitrogen atom to which they bond toform a 5- or 6-membered saturated heterocyclic group with or withoutbeing intervened with nitrogen, oxygen or sulfur atom wherein theheterocyclic group has optionally a substituent selected from oxo, alower alkyl, a lower alkanoyl, and carbamoyl), and a group of theformula: ##STR71## (n is as defined above, and R¹⁴ and R¹⁵ are the sameor different and are each hydrogen atom, a lower alkyl, a lower alkenyl,a lower alkanoyl, a cycloalkyl, an oxiranyl-substituted lower alkyl, alower alkyl having 1 to 2 substituents selected from a lower alkoxy,hydroxy and an amino having optionally a lower alkyl substituent, aphenyl-lower alkyl, a pyridyl-lower alkyl, a lower alkylsulfonyl,benzoyl, a lower alkoxycarbonyl, anilinocarbonyl, an aminocarbonylhaving optionally a lower alkyl substituent, a cyano-substituted loweralkyl, a lower alkoxycarbonyl-substituted lower alkyl, acarbamoyl-substituted lower alkyl, a carboxy-substituted lower alkyl, atetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent on the piperidinyl ring, ahalogen-substituted lower alkanoyl, an imidazolyl-substituted loweralkanoyl, an amino-lower alkanoyl having optionally a substituentselected from a lower alkyl and a lower alkoxycarbonyl, anaminocarbonyl-lower alkyl having optionally a lower alkyl substituent,or a phenyl-lower alkoxycarbonyl, or R¹⁴ and R¹⁵ may bind together withthe nitrogen atom to which they bond to form a 5- or 6-memberedsaturated heterocyclic group with or without being intervened withnitrogen or oxygen atom, which heterocyclic group may optionally have asubstituent selected from a lower alkyl, a phenyl-lower alkyl and alower alkanoyl.

The reaction of the compound (1OO) and the compound (60) is carried outin an appropriate solvent in an autoclave. The solvent includes anysolvent as used in the reaction of the compound (7) and the compound (8)in the above Reaction Scheme-4. The reaction is usually carried out at atemperature of from room temperature to about 200° C., preferably fromroom temperature to about 150° C., for about 1 to 7 hours.

The subsequent deamination reaction is carried out in an appropriatesolvent in the presence of a basic compound. The solvent includes thesame solvent as used in the above reaction of the compound (1OO) and thecompound (60). The basic compound includes any basic compound as used inthe reaction of converting the compound (1A) into the compound (1EE) inthe above Reaction Scheme-38. The reaction is usually carried out at atemperature of from room temperature to about 150° C., preferably fromroom temperature to about 100° C., for about 1 to 10 hours. ##STR72##wherein R¹, R², R³, R¹⁴, M, and W' are as defined above, R⁷⁸ is anoxiranyl-substituted lower alkyl, R⁷⁹ is a lower alkoxy, or an aminohaving optionally a lower alkyl substituent, and R⁸⁰ is a lower alkylhaving 2 substituents selected from hydroxy, a lower alkoxy, and anamino having optionally a lower alkyl substituent.

The reaction of the compound (1QQ) and the compound (61) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reaction of the compound (1QQ) and the compound (62) can be carriedout by firstly reacting them in trifluoroacetic acid at a temperature ofabout 0° C. to about 100° C., preferably about 0° C. to about 50° C.,for about 1 to 7 hours, followed by hydrolysis of the resultant.

The hydrolysis is carried out in an appropriate solvent or withoutsolvent in the presence of an acid or a basic compound. The solventincludes, for example, water, lower alcohols (e.g. methanol, ethanol,isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.),ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether,etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixtureof these solvents. The acid includes, for example, mineral acids (e.g.hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids(e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.), and thelike. The basic compound includes, for example, metal carbonates (e.g.sodium carbonate, potassium carbonate, etc.), metal hydroxides (e.g.sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.). Thereaction is usually carried out at a temperature of from roomtemperature to about 200° C., preferably from room temperature to about150° C., for about 0.5 to 25 hours. ##STR73## wherein R¹, R², R³, and W'are as defined above, and R⁸¹ is hydroxyimino or a loweralkanoyloxyimino.

The reaction of converting the compound (1SS) into the compound (1ll) iscarried out by catalytically hydrogenating the compound (1SS) in anappropriate solvent in the presence of a catalyst. The solvent includes,for example, water, acetic acid, alcohols (e.g. methanol, ethanol,isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.),ethers (e.g. diethylene glycol dimethyl ether, dioxane, tetrahydrofuran,diethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.),aprotic polar solvents (e.g. dimethylformamide, etc.), or a mixture ofthese solvents. The catalyst includes, for example, palladium, palladiumblack, palladium-carbon, platinum, platinum oxide, copper chromate,Raney nickel, and the like. The catalyst is usually used in an amount of0.02 to 1 part by weight to 1 part by weight of the compound (1SS). Thereaction is usually carried out at a temperature of from about -20° C.to about 100° C., peferably about 0° C. to about 70° C., under ahydrogen atmospheric pressure of 1 to 10 atm. for about 0.5 to 20 hours.

Alternatively, the reducing reaction can also be carried out by using ahydrogenating reducing agent. The hydrogenating reducing agent includes,for example, lithium aluminum hydride, sodium boro hydride, diborane,etc. The reducing agent is usually used in an amount of at least onemole, preferably 1 to 10 moles, to 1 mole of the compound (1SS). Thereaction is usually carried out in an appropriate solvent, such aswater, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.),ethers (e.g. tetrahydrofuran, diethyl ether, diglyme, etc.), aceticacid, and the like, at a temperature of about 0° C. to about 200° C.,preferably about 0° C. to 170° C., for about 10 minutes to about 10hours. When lithium aluminum hydride or diborane is used as the reducingagent, it is preferable to use an anhydrous solvent such as diethylether, tetrahydrofuran, diglyme, etc. ##STR74## wherein R¹, R², R³, W',l, R^(14a) are as defined above, and R⁸³ is phenyl or a lower alkyl.

The reaction of the compound (1K) and the compound (63) can be carriedout under the same conditions as in the reaction of the compound (2b)and the compound (38) in the above Reaction Scheme-26. ##STR75## whereinR¹, R², R³, W', l, R^(14a) are as defined above.

The reaction of the compound (1K) and the glyconitrile (64) can becarried out in an appropriate solvent. The solvent includes the samesolvent as used in the reaction of the compound (7) and the compound (8)in the above Reaction Scheme-4. The reaction is usually carried out at atemperature of from about 0° C. to about 150° C., preferably about 0° C.to about 100° C., for about 1 to 10 hours. The glyconitrile (64) is usedin an amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole ofthe compound (1K). ##STR76## wherein R¹, R², R³, W', l, R^(14a) are asdefined above, R⁸⁴ is a lower alkoxycarbonyl-substituted lower alkyl,R⁸⁵ is an amino having optionally a lower alkyl substituent, R⁸⁶ is anaminocarbonyl-lower alkyl having optionally a lower alkyl substituent,and R⁸⁷ is a carboxy-substituted lower alkyl.

The reaction of the compound (1VV) and the compound (65) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The hydrolysis reaction of the compound (1VV) can be carried out underthe same conditions as in the hydrolysis reaction of the compound (1QQ)and the compound (62) in the above Reaction Scheme-41. ##STR77## whereinR¹, R², R³, W', l, X, and R^(14a) are as defined above, R⁸⁸ is atetrahydropyranyloxy-substituted lower alkyl, R⁸⁹ is a loweralkanoyloxy-substituted lower alkyl, R⁹⁰ is a hydroxy-substituted loweralkyl, and R⁹¹ is a lower alkanoyl.

The reaction of the compound (1YY) and the compound (66) can be carriedout in a solvent such as acetic acid at a temperature of about 0° C. toabout 200° C., preferably about 0° C. to about 150° C., for about 0.5 to15 hours.

The hydrolysis reaction of the compound (1YY) can be carried out underthe same conditions as in the hydrolysis reaction of the compound (1QQ)and the compound (62) in the above Reaction Scheme-41, wherein apyridinium salt (e.g. pyridinium p-toluenesulfonate, etc.) may be usedas the acid. ##STR78## wherein R¹, R², R³, W', and R²⁶ are as definedabove.

The reaction of converting the compound (1A) into the compound (1bbb)can be carried out under the same conditions as in the reaction ofconverting the compound (1A) into the compound (1C) in the aboveReaction Scheme-15. ##STR79## wherein R¹, R², R³ and W' are as definedabove, R⁹² and R⁹³ are each a lower alkoxy.

The reaction of the compound (1ll) and the compound (68) is carried outin an appropriate solvent in the presence of an acid. The solventincludes, for example, water, alcohols (e.g. methanol, ethanol,isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.),ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether,etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixtureof these solvents. The acid includes, for example, mineral acids (e.g.hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids(e.g. formic acid, acetic acid, aromatic sulfonic acids, etc.). Thereaction is usually carried out at a temperature of from roomtemperature to about 200° C., preferably from room temperature to about150° C., for about 0.5 to 5 hours. The compound (68) is usually used inan amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole of thecompound (1ll). ##STR80## wherein R¹, R², R³, W', and R^(14a) are asdefined above, R⁹⁴ is a halogen-substituted lower alkanoyl, R⁹⁵ is animidazolyl-substituted lower alkanoyl or an amino-lower alkanoyl havingoptionally a substituent selected from a lower alkyl and a loweralkoxycarbonyl, and R⁹⁶ is imidazolyl, or an amino having optionally asubstituent selected from a lower alkyl and a lower alkoxycarbonyl.

The reaction of the compound (1ddd) and the compound (69) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. ##STR81## wherein R¹,R², R³, and W' are as defined above, R⁹⁷ is a lower alkanoyloxy having ahalogen substituent, R⁹⁸ is an amino having optionally a lower alkylsubstituent, and R⁹⁹ is an amino-lower alkanoyloxy having optionally alower alkyl substituent.

The reaction of the compound (1fff) and the compound (70) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. ##STR82## wherein R¹,R², R³, W', R⁸², and R⁸³ are as defined above, R¹⁰⁰ is acarboxy-substituted lower alkoxy, and R¹⁰¹ is a group of the formula:##STR83## (A, R⁸² and R⁸³ are as defined above).

The reaction of the compound (1hhh) and the compound (71) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. ##STR84## wherein R¹,R², R³, W", X, and R⁸² are as defined above, and R¹⁰² is hydrogen atomor a lower alkyl, provided that in the compound (1jjj), the groups ofthe formulae: --NH--R¹⁰² and --OH are substituted at the positionsadjacent each other.

The reaction of the compound (1jjj) and the compound (72) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. ##STR85## wherein R¹,R², R³, W', R²⁶ and X are as defined above, and R¹⁰⁴ is a lower alkyl.

The reaction of the compound (1A) and the compound (73) can be carriedout in an appropriate solvent. The solvent includes, for example, ethers(diethyl ether, dioxane, tetrahydrofuran, etc.), aromatic hydrocarbons(e.g. benzene, toluene, xylene, etc.), saturated hydrocarbons (e.g.pentane, hexane, heptane, cyclohexane, etc.), or a mixture of thesesolvents. The reaction is usually carried out at a temperature of fromabout -70° C. to about 50° C., preferably from about -30° C. to roomtemperature, for about 1 to 6 hours. The compound (73) is used in anamount of at least 1 mole, preferably 1 to 5 moles, to 1 mole of thecompound (1A). ##STR86## wherein R¹, R², R³, W', R^(58'), R^(59'), and Aare as defined above, and R¹⁰⁵ is a lower alkylsulfonyloxy.

The reaction of the compound (1mmm) and the compound (74) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

Among the active compounds (1) of this invention, the compounds havingan acidic group can easily be converted into salts by treating with apharmaceutically acceptable basic compound. The basic compound includes,for example, metal hydroxides such as sodium hydroxide, potassiumhydroxide, lithium hydroxide, calcium hydroxide, etc., alkali metalcarbonates or hydrogen carbonates such as sodium carbonate, sodiumhydrogen carbonate, etc., alkali metal alcoholates such as sodiummethylate, potassium ethylate, etc. Besides, among the active compounds(1) of this invention, the compounds having a basic group can easily beconverted into acid addition salts thereof by treating with apharmaceutically acceptable acid. The acid includes, for example,inorganic acids such as sulfuric acid,-nitric acid, hydrochloric acid,hydrobromic acid, etc., and organic acids such as acetic acid,p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid,fumaric acid, citric acid, succinic acid, benzoic acid, etc. These saltsare useful as an active ingredient as like as the compounds (1) in thefree form.

In addition, the compounds (1) of this invention include stereoisomersand optical isomers, and these isomers are also useful as the activeingredient in this invention.

The compounds of this invention thus obtained can easily be isolated andpurified by conventional isolation methods. The isolation methods are,for example, distillation method, recrystallization method, columnchromatography, ion exchange chromatography, gel chromatography,affinity chromtography, preparative thin layer chromatography,extraction with a solvent, and the like.

The compounds and their salts of this invention are useful as avasopressin antagonist and are used in the form of a conventionalpharmaceutical preparation. The preparation is prepared by usingconventional dilutents or carriers such as fillers, thickening agents,binders, wetting agents, disintegrators, surfactants, lubricants, andthe like. The pharmaceutical preparations may be selected from variousforms in accordance with the desired utilities, and the representativeforms are tablets, pills, powders, solutions, suspensions, emulsions,granules, capsules, suppositories, injections (solutions, suspensions,etc.), and the like. In order to form in tablets, there are usedcarriers such as vehicles (e.g. lactose, white sugar, sodium chloride,glucose, urea, starches, calcium carbonate, kaolin, crystallinecellulose, silicic acid, etc.), binders (e.g. water, ethanol, propanol,simple syrup, glucose solution, starch solution, gelatin solution,carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate,polyvinylpyrrolidone, etc.), disintegrators (e.g. dry starch, sodiumarginate, agar powder, laminaran powder, sodium hydrogen carbonate,calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodiumlaurylsulfate, stearic monoglyceride, starches, lactose, etc.),disintegration inhibitors (e.g. white sugar, stearin, cacao butter,hydrogenated oils, etc.), absorption promoters (e.g. quaternary ammoniumbase, sodium laurylsulfate, etc.), wetting agents (e.g. glycerin,starches, etc.), adsorbents (e.g. starches, lactose, kaolin, bentonite,colloidal silicates, etc.), lubricants (e.g. purified talc, stearates,boric acid powder, polyethylene glycol, etc.), and the like. Moreover,the tablets may also be in the form of a conventional coated tablet,such as sugar-coated tablets, gelatin-coated tablets, enteric coatedtablets, film coating tablets, or double or multiple layer tablets. Inthe preparation of pills, the carriers include vehicles (e.g. glucose,lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin,talc, etc.), binders (e.g. gum arabic powder, tragacanth powder,gelatin, ethanol, etc.), disintegrators (e.g. laminaran, agar, etc.),and the like. In the preparation of suppositories, the carriers include,for example, polyethylene glycol, cacao butter, higher alcohols, higheralcohol esters, gelatin, semi-synthetic glycerides, and the like.Capsules can be prepared by charging a mixture of the compound of thisinvention with the above carriers into hard gelatin capsules or softcapsules in a usual manner. In the preparation of injections, thesolutions, emulsions or suspendions are sterilized and are preferablymade isotonic with the blood. In the preparation of these solutions,emulsions and suspensions, there are used conventional diluents, such aswater, ethyl alcohol, macrogol (propylene glycol), ethoxylatedisostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylenesorbitan fatty acid esters, and the like. In this case, thepharmaceutical preparations may also be incorporated with sodiumchloride, glucose, or glycerin in an amount sufficient to make themisotonic, and may also be incorporated with conventional solubilizers,buffers, anesthetizing agents. Besides, the pharmaceutical preparationsmay optionally be incorporated with coloring agents, preservatives,perfumes, flavors, sweeting agents, and other medicaments, if required.

The amount of the active compound of this invention (active ingredient)to be incorporated into the anti-vasopressin preparations is notspecified but may be selected from a broad range, but usually, it ispreferably in the range of 1 to 70% by weight, more preferably 5 to 50%by weight.

The anti-vasopressin preparation of this invention may be administeredin any method, and suitable method for administration may be determinedin accordance with various forms of preparation, ages, sexes and otherconditions of the patients, the degree of severity of diseases, and thelike. For instance, tablets, pills, solutions, suspensions, emulsions,granules and capsules are administered orally. The injections areintraveneously administered alone or together with a conventionalauxiliary liquid (e.g. glucose, amino acid solutions), and further areoptionally administered alone in intramuscular, intracutaneous,subcutaneous, or intraperitoneal route, if required. Suppositories areadministered in intrarectal route.

The dosage of the anti-vasopressin agent of this invention may beselected in accordance with the usage, ages, sexes and other conditionsof the patients, the degree of severity of the diseases, and the like,but is usually in the range of about 0.6 to 50 mg of the active compoundof this invention per 1 kg of body weight of the patient per day. Theactive compound is preferably contained in an amount of 10 to 1000 mgper the dosage unit.

BRIEF DESCRIPTION OF DRAWING

FIG. 1 to FIG. 4 show a chart of NMR (CDCl₃) of the compounds inExamples 978 and 979.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention is illustrated by the following Preparations ofanti-vasopressin agent, Reference Examples of processes for preparingthe starting compounds to be used for preparing the active compounds,Examples of processes for preparing the active compounds, andExperiments of the activities of the active compounds of this invention.

Preparation 1

Film coated tablets are prepared from the following components.

    ______________________________________                                        Components                Amount                                              ______________________________________                                        4-Methylamino-1-[4-(3,5-dichlorobenzoyl-                                                                150    g                                              amino)benzoyl]-1,2,3,4-tetrahydroquinoline                                    Avicel (tradename of microcrystalline cellulose, 40 g                         manufactured by Asahi Chemical Industry                                       Co., Ltd., Japan)                                                             Corn starch 30 g                                                              Magnesium stearate 2 g                                                        Hydroxypropyl methylcellulose 10 g                                            Polyethylene glycol-6000 3 g                                                  Castor oil 40 g                                                               Ethanol 40 g                                                                ______________________________________                                    

The active component of this invention, Avicel, corn starch andmagnesium stearate are mixed and kneaded and the mixture is tablettedusing a conventional pounder (R 10 mm) for sugar coating. The tabletsthus obtained are coated with a film coating agent consisting ofhydroxypropyl methylcellulose, polyethylene glycol-6000, castor oil andethanol to give film coated tablets.

Preparation 2

Tablets are prepared from the following components.

    ______________________________________                                        Components                Amount                                              ______________________________________                                        1-[4-(N-Butylanilinoacetylamino)benzoyl]-                                                               150    g                                              2,3,4,5-tetrahydroy-1H-benzazepine                                            Citric acid 1.0 g                                                             Lactose 33.5 g                                                                Dicalcium phosphate 70.0 g                                                    Pullonic F-68 30.0 g                                                          Sodium laurylsulfate 15.0 g                                                   Polyvinylpyrrolidone 15.0 g                                                   Polyethylene glycol (Carbowax 1500) 4.5 g                                     Polyethylene glycol (Carbowax 6000) 45.0 g                                    Corn starch 30.0 g                                                            Dry sodium stearate 3.0 g                                                     Dry magnesium stearate 3.0 g                                                  Ethanol  q.s.                                                               ______________________________________                                    

The active compound of this invention, citric acid, lactose, dicalciumphosphate, Pullonic F-68 and sodium laurylstearate are mixed. Themixture is screened with No. 60 screen and is granulated with an alcoholsolution containing polyvinylpyrrolidone, carbowax 1500 and 6000. Ifrequired, an alcohol is added thereto so that the powder mixture is madea paste-like mass. Corn starch is added to the mixture and the mixtureis continuously mixed to form uniform particles. The resulting particlesare passed through No. 10 screen and entered into a tray and then driedin an oven at 100° C. for 12 to 14 hours. The dried particles arescreened with No. 16 screen and thereto are added dry sodiumlaurylsulfate and dry magnesium stearate, and the mixture is tablettedto form the desired shape.

The core tablets thus prepared are vanished and dusted with talc inorder to guard from wetting. Undercoating is applied to the coretablets. In order to administer the tablets orally, the core tablets arevanished several times. In order to give round shape and smooth surfaceto the tablets, further undercoating and coating with lubricant areapplied thereto. The tablets are further coated with a coloring coatingmaterial until the desired colored tablets are obtained. After drying,the coated tablets are polished to obtain the desired tablets havinguniform gloss.

Preparation 3

An injection preparation is prepared from the following components.

    ______________________________________                                        Components                Amount                                              ______________________________________                                        4-Methyl-1-[4-(2,3-dimethylbenzoyl-                                                                     5      g                                              amino)benzoyl]-2,3,4,5-tetrahydro                                             1H-1,4-benzodiazepine                                                         Polyethylene qlycol (molecular weight: 4000) 0.3 g                            Sodium chloride 0.9 g                                                         Polyoxyethylene sorbitan monooleate 0.4 g                                     Sodium metabisulfite 0.1 g                                                    Methyl-paraben 0.18 g                                                         Propyl-paraben 0.02 g                                                         Distilled water for injection 10.0 ml                                       ______________________________________                                    

The above parabens, sodium metabisulfite and sodium chloride aredissolved in distilled water of half volume of the above with stirringat 80° C. The solution thus obtained is cooled to 40° C., and the activecompound of this invention and further polyethylene glycol andpolyoxyethylene sorbitan monooleate are dissolved in the above solution.To the solution is added distilled water for injection to adjust to thedesired volume, and the solution is sterilized by filtering with anappropriate filter paper to give an injection preparation.

REFERENCE EXAMPLE 1

To a solution of 1,2,3,4-tetrahydroquinoline (28.7 g) in acetone (400ml) and water (200 ml) is added potassium carbonate (38.8 g), andthereto is added p-nitrobenzoyl chloride (40 g) under ice-cooling andthe mixture is stirred at room temperature overnight. To the reactionmixture is added a suitable amount of water. The precipitated crystal iscollected by filtration and dried to give1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline (40.8 g) as white powder,m.p. 86-88° C.

REFERENCE EXAMPLE 2

To a solution of 10% Pd-C (5 g) in ethanol (500 ml) is added1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline (53.4 g) and the mixtureis subjected to catalytic reduction at ordinary temperature underatmospheric pressure of hydrogen. After the reduction, 10% Pd-C isremoved by filtration, and the filtrate is concentrated under reducedpressure to give 1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline (46.7 g)as yellow powder, m.p. 185-188° C.

REFERENCE EXAMPLE 3

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

1-(3-Nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, white powder, m.p.134-136° C.

1-(2-Nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder, m.p.152-154° C.

3-Methyl-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 109-110° C.

4-Methyl-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 134-136° C.

2-Methyl-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 143-145° C.

1-(4-Nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, yellow powder,m.p. 143-145° C.

1-(3-Methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder, m.p. 100-102° C.

1-(3-Methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, yellowpowder, m.p. 146-148° C.

1-(4-Nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine, white powder, m.p.83-85° C.

1-(4-Nitrobenzoyl)-3,4-dihydro-2H-1,4-benzoxazine, yellow powder, m.p.167-169° C.

1-(4-Nitrobenzoyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine, yellow powder,m.p. 196-198° C.

1-(4-Nitrobenzoyl)-4-methyl-1,2,3,4-tetrahydroquinoxaline, brown powder

¹ H-NMR (CDCl₃) δ: 3.03 (3H, s), 3.54 (2H, t, J=5.7 Hz), 4.06 (2H, t,J=5.7 Hz), 6.2-6.5 (2H, m), 6.70 (1H, d, J=8.2 Hz), 6.9-7.1 (1H, m),7.54 (2H, d, J=8.8 Hz), 8.13 (2H, d, J=8.8 Hz)

1-(4-Nitrobenzoyl)-5-methyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.7-2.0 (1H, m), 2.0-2.3 (1H, m), 2.8-3.0 (1H, m),2.98 (3H, s), 3.0-3.2 (1H, m), 3.4-3.6 (1H, m), 4.6-4.8 (1H, m), 6.5-6.7(2H, m), 6.94 (1H, d, J=8.1 Hz), 7.1-7.2 (1H, m), 7.33 (2H, d, J=8.9Hz), 7.97 (2H, d, J=8.9 Hz)

1-(4-Nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,brown oil

¹ H-NMR (CDCl₃) δ: 2.44 (3H, s), 3.0-3.3 (3H, m), 3.77 (1H, d, J=13.7Hz), 4.06 (1H, d, J=13.6 Hz), 4.9-5.1 (1H, m), 6.59 (1H, d, J=7.7 Hz),6.97 (1H, t, J=7.6 Hz), 7.15 (1H, t, J=7.4 Hz), 7.2-7.5 (3H, m), 8.03(2H, d, J=8.8 Hz)

1-(3-Methoxy-4-nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 146-148° C.

1-(4-Nitrobenzoyl)-4-n-propyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 131-133° C.

1-(4-Nitrobenzoyl)-5-chloro-1,2,3,4-tetrahydroquinoline, white powder,m.p. 134-136° C.

1-(4-Nitrobenzoyl)-6-methoxy-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 149-151° C.

1-(4-Nitrobenzoyl)-6-methyl-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 109-110° C.

1-(4-Nitrobenzoyl)-7-methoxy-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 139-141° C.

1-(4-Nitrobenzoyl)-3-(4-methyl-1-piperazinyl)-1,2,3,4-tetrahydroquinoline,yellow amorphous

¹ H-NMR (CDCl₃) δ: 2.29 (3H, s), 2.35-3.20 (11H, m), 3.86-4.15 (2H, m),6.48-6.63 (1H, m), 6.89 (1H, t, J=7.4 Hz), 7.05 (1H, t, J=7.4 Hz), 7.22(1H, d, J=7.4 Hz), 7.52 (2H, d, J=8.8 Hz), 8.11 (2H, d, J=8.8 Hz)

1-(4-Nitrobenzoyl)-3-(1-pyrrolidinyl)-1,2,3,4-tetrahydroquinoline,yellow amorphous

¹ H-NMR (CDCl₃) δ: 1.70-1.95 (4H, m), 2.52-3.30 (7H, m), 3.80-4.22 (2H,m), 6.52 (1H, brs), 6.88 (1H, t, J=7.6 Hz), 6.96-7.11 (1H, m), 7.20 (2H,d, J=7.6 Hz), 7.54 (2H, d, J=8.8 Hz), 8.12 (2H, d, J=8.8 Hz)

1-(4-Nitrobenzoyl)-4-oxo-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 189-190° C.

1-(4-Nitrobenzoyl)-3-hydroxymethyl-1,2,3,4-tetrahydroquinoline, yellowpowder, m.p. 97-100° C.

1-(4-Nitrobenzoyl)-3-ethoxycarbonyl-1,2,3,4-tetrahydroquinoline, paleyellow powder, m.p. 162-163° C.

1-(4-Nitrobenzoyl)-4-dimethylamino-1,2,3,4-tetrahydroquinoline, lightbrown oil

¹ H-NMR (CDCl₃) δ: 1.80-2.02 (1H, m), 2.20-2.50 (7H, m), 3.47 (1H, t,J=4.9 Hz), 3.70-3.88 (1H, m), 4.06-4.25 (1H, m), 6.46 (1H, d, J=7.5 Hz),6.89 (1H, t, J=7.5 Hz), 7.05 (1H, t, J=7.5 Hz), 7.34 (1H, d, J=7.5 Hz),7.50 (2H, d, J=7.0 Hz), 8.10 (2H, d, J=7.0 Hz)

REFERENCE EXAMPLE 4

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

1-(3-Aminobenzoyl)-1,2,3,4-tetrahydroquinoline, white powder, m.p.128-130° C.

1-(2-Aminobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder

¹ H-NMR (CDCl₃) δ: 2.01 (2H, quint, J=6.6 Hz), 2.81 (2H, t, J=6.6 Hz),3.86 (2H, t, J=6.4 Hz), 4.6-4.8 (2H, m), 6.43 (1H, t, J=7 Hz), 6.66 (1H,d, J=8 Hz), 6.79 (1H, dd, J=1.4 Hz, J=7.6 Hz), 6.8-7.2 (5H, m)

3-Methyl-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 197-200° C.

4-Methyl-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 197-199° C.

2-Methyl-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 204-206° C.

1-(4-Aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, yellow powder,m.p. 172-174° C.

1-(3-Methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder, m.p. 156-158° C.

1-(3-Methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder, m.p. 165-167° C.

1-(4-Aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine, white powder, m.p.177-179° C.

1-(4-Aminobenzoyl)-3,4-dihydro-2H-1,4-benzoxazine, white powder, m.p.192-194° C.

1-(4-Aminobenzoyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine, yellow powder,m.p. 196-198° C.

1-(4-Aminobenzoyl)-4-methyl-1,2,3,4-tetrahydroquinoxaline, yellowpowder, m.p. 210-212° C.

1-(4-Aminobenzoyl)-5-methyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine,white powder, m.p. 159-161° C.

1-(4-Aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,brown powder, m.p. 169-171° C.

1-(3-Methoxy-4-aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 2.41 (3H, s), 2.9-3.2 (3H, m), 3.61 (3H, s), 3.6-4.2(4H, m), 4.8-5.2 (1H, m), 6.38 (1H, d, J=8.1 Hz), 6.6-6.8 (3H, m),6.9-7.2 (2H, m), 7.2-7.4 (1H, m)

1-(4-Aminobenzoyl)-4-n-propyl-2,3,4,5-tetrahydro-1H-1,4-benzazepine,brown powder, m.p. 151-153° C.

1-(4-Aminobenzoyl)-5-chloro-1,2,3,4-tetrahydroquinoline, white powder,m.p. 174-175° C.

1-(4-Aminobenzoyl)-6-methoxy-1,2,3,4-tetrahydroquinoline, pale yellowpowder, m.p. 159-160° C.

1-(4-Aminobenzoyl)-6-methyl-1,2,3,4-tetrahydroquinoline, white powder,m.p. 145-146° C.

1-(4-Aminobenzoyl)-7-methoxy-1,2,3,4-tetrahydroquinoline, pale yellowpowder, m.p. 150-152° C.

1-(4-Aminobenzoyl)-3-(4-methyl-1-piperazinyl)-1,2,3,4-tetrahydroquinoline,light beige powder, m.p. 157-159° C.

1-(4-Aminobenzoyl)-3-(1-pyrrolidinyl)-1,2,3,4-tetrahydroquinoline, paleyellow powder, m.p. 173-174.5° C.

1-(4-Aminobenzoyl)-2,3-dihydro-4(1H)-quinolinone, pale yellow powder,m.p. 178-180° C.

1-(4-Aminobenzoyl)-3-hydroxymethyl-1,2,3,4-tetrahydroquinoline, whitepowder, m.p. 179-181° C.

1-(4-Aminobenzoyl)-3-ethoxycarbonyl-1,2,3,4-tetrahydroquinoline, paleyellow amorphous

¹ H-NMR (CDCl₃) δ: 1.21 (3H, t, J=7.1 Hz), 3.00-3.24 (3H, m), 3.70-4.30(6H, m), 6.48 (2H, d, J=8.5 Hz), 6.69 (1H, d, J=7.9 Hz), 6.77-7.30 (5H,m)

1-(4-Aminobenzoyl)-4-dimethylamino-1,2,3,4-tetrahydroquinoline, brownoil

¹ H-NMR (CDCl₃) δ: 1.83-2.05 (1H, m), 2.13-2.30 (1H, m), 2.34 (6H, m),3.55-3.83 (2H, m), 3.89 (1H, brs), 3.97-4.18 (1H, m), 6.47 (2H, d, J=7.0Hz), 6.68 (1H, d, J=7.9 Hz), 6.85-7.05 (2H, m), 7.20 (2H, d, J=7.0 Hz),7.37 (1H, d, J=7.4 Hz)

REFERENCE EXAMPLE 5

To terephthalic acid monomethyl ester (15 g) is added thionyl chloride(100 ml) and the mixture is refluxed for 2 hours. The thionyl chlorideis distilled off under reduced pressure to give terephthalic acidchloride monomethyl ester. Separately, to a solution of1,2,3,4-tetrahydroquinoline (14.4 g) in dichloromethane (200 ml) isadded triethylamine (16.9 g) and further thereto is added slowlyterephthalic acid chloride monomethyl ester obtained above underice-cooling. Then, the mixture is stirred at room temperature for 1hour. After completion of the reaction, water is added to the reactionmixture. The mixture is extracted with dichloromethane and dried overmagnesium sulfate. The solvent is distilled off under reduced pressureand the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane) to give1-(4-methoxycarbonylbenzoyl)-1,2,3,4-tetrahydroquinoline (22.7 9) aswhite powder, m.p. 72-74° C.

REFERENCE EXAMPLE 6

To a solution of1-(4-methoxycarbonylbenzoyl)-1,2,3,4-tetrahydroquinoline (22.7 g) inmethanol (300 ml) is added 5% aqueous sodium hydroxide solution (150 ml)and the mixture is refluxed for 2 hours. Methanol is distilled off underreduced pressure and the resulting residue is acidified with dilutedhydrochloric acid, extracted with diethyl ether, and dried overmagnesium sulfate. The solvent is distilled off under reduced pressureand the resulting crystal is collected by filtration to give1-(4-carboxybenzoyl)-1,2,3,4-tetrahydroquinoline (13.2 g) as whitepowder, m.p. 181-183° C.

REFERENCE EXAMPLE 7

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

5-Dimethylamino-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,pale yellow powder, m.p. 139-142° C.

5-Dimethylamino-1-(3-methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 139-141° C.

4-(N-Methyl-N-ethylamino)-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline,pale yellow oil

¹ H-NMR (CDCl₃) δ: 1.11 (3H, t, J=7.1 Hz), 1.90-2.25 (2H, m), 2.30 (3H,s), 2.57 (2H, q, J=7.1 Hz), 3.55-3.85 (2H, m), 4.00-4.21 (1H, m),6.35-6.60 (1H, m), 6.80-6.98 (1H, t, J=7.9 Hz), 7.00-7.15 (1H, m),7.33-7.60 (3H, m), 8.10 (2H, d, J=8.8 Hz)

4-Dimethylamino-1-(3-methoxy-4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline,brown oil

¹ H-NMR (CDCl₃) δ: 1.80-2.05 (1H, m), 2.33 (6H, s), 2.30-2.50 (1H, m),3.40-3.52 (1H, m), 3.78 (3H, s), 3.70-3.88 (1H, m), 4.04-4.24 (1H, m),6.52 (1H, d, J=8.2 Hz), 6.85-7.13 (4H, m), 7.28-7.38 (1H, m), 7.71 (1H,d, J=8.2 Hz)

1-(4-Nitrobenzoyl)-4-ethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.16 (3H, t, J=7.1 Hz), 2.5-2.7 (2H, m), 3.0-3.3 (3H,m), 3.98 (2H, q, J=14 Hz), 4.8-5.0 (1H, m), 6.59 (1H, d, J=7.7 Hz), 6.96(1H, t, J=7.7 Hz), 7.14 (1H, t, J=7.4 Hz), 7.2-7.4 (3H, m), 8.02 (2H, d,J=8.8 Hz)

1-(4-Nitrobenzoyl)-4-isopropyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 222-223° C.

1-(4-Nitrobenzoyl)-4-cyclohexyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,brown oil

¹ H-NMR (CDCl₃) δ: 1.0-1.5 (5H, m), 1.5-2.1 (5H, m), 2.4-2.7 (1H, m),2.9-3.3 (3H, m), 3.94 (2H, s), 4.9-5.1 (1H, m), 6.57 (1H, d, J=7.7 Hz),6.8-7.0 (1H, m), 7.0-7.2 (1H, m), 7.2-7.4 (3H, m), 8.01 (2H, d, J=8.8Hz)

1-(4-Nitrobenzoyl)-5-methyl-1,2,3,4,5,6-hexahydro-1,5-benzodiazocine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.5-2.1 (2H, m), 2.40 (3H, s), 2.3-2.6 (1H, m),2.8-3.2 (2H, m), 3.50 (1H, d, J=13.4 Hz), 3.84 (1H, d, J=13.4 Hz),4.8-5.0 (1H, m), 7.0-7.3 (4H, m), 7.41 (2H, d, J=8.9 Hz), 8.00 (2H, d,J=8.9 Hz)

1-(4-Nitrobenzoyl)-1,2,3,4-tetrahydro-5,1-benzoxazepine, white powder,m.p. 144.5-145.5° C.

1-(2-Nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 177-180° C.

1-(3-Nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 145-146° C.

6-Fluoro-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow needles,m.p. 145-146° C.

REFERENCE EXAMPLE 8

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

5-Dimethylamino-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 120-122° C.

5-Dimethylamino-1-(3-methoxy-4-amino)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 121-123° C.

4-(N-Methy-N-ethylamino)-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline,orange amorphous

¹ H-NMR (CDCl₃) δ: 1.11 (3H, t, J=7.1 Hz), 1.90-2.20 (2H, m), 2.28 (3H,s), 2.26 (2H, q, J=7.1 Hz), 3.60-4.25 (5H, m), 6.48 (2H, d, J=8.5 Hz),6.69 (1H, d, J=7.9 Hz), 6.80-7.05 (2H, m), 7.24 (2H, d, J=8.5 Hz), 7.46(1H, d, J=6.2 Hz)

4-Dimethylamino-1-(3-methoxy-4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline,pale yellow amorphous

¹ H-NMR (CDCl₃) δ: 1.83-2.04 (1H, m), 2.15-2.32 (1H, m), 2.33 (6H, s),3.50-3.82 (2H, m), 3.64 (3H, s), 3.95-4.18 (3H, m), 6.50 (1H, d, J=7.9Hz), 6.65 (1H, dd, J=7.9 Hz, 1.1 Hz), 6.78-7.03 (4H, m), 7.34 (1H, dd,J=7.5 Hz, 1.5 Hz)

1-(4-Aminobenzoyl)-4-ethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder, m.p. 186-188° C.

1-(4-Aminobenzoyl)-4-isopropyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder, m.p. 191-192° C.

1-(4-Aminobenzoyl)-4-cyclohexyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder, m.p. 149.5-150.5° C.

1-(4-Aminobenzoyl)-5-methyl-1,2,3,4,5,6-hexahydro-1,5-benzodiazocine,yellow powder, m.p. 143-145° C.

1-(4-Aminobenzoyl)-1,2,3,4-tetrahydro-5,1-benzoxazepine, yellow powder,m.p. 163.5-164.5° C.

1-(2-Aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 144-146° C.

1-(3-Aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder, mp. 153-155° C.

6-Fluoro-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline, white powder,m.p. 160.5-161.5° C.

REFERENCE EXAMPLE 9

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

1-(2-Chloro-4-nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

¹ H-NMR (CDCl₃) δ: 2.40 (3H, s), 2.96-3.33 (3H, m), 3.60-3.79 (1H, m),3.96-4.23 (1H, m), 4.70-4.91 (1H, m), 6.80-7.43 (5H, m), 7.80-7.99 (1H,m), 8.08-8.21 (1H, m)

1-(3-Methyl-4-nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

¹ H-NMR (CDCl₃) δ: 2.43 (3H, s), 2.48 (3H, s), 2.92-3.28 (3H, m), 3.91(2H, AB-q, J=13.9 Hz, 45.5 Hz), 4.77-5.01 (1H, m), 6.54-6.70 (1H, m),6.88-7.37 (5H, m), 7.62-7.78 (1H, m)

5-Dimethylamino-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

¹ H-NMR (CDCl₃) δ: 1.23-2.57 (10H, m), 2.68-5.15 (3H, m), 6.79-7.45 (4H,m), 7.49-8.39 (3H, m)

5-Oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, white powder(ethyl acetate/n-hexane), m.p. 147-148° C.

5-Hydroxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder (ethyl acetate/n-hexane), m.p. 148-150° C.

5-Methoxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ: 1.47-2.48 (4H, m), 2.70-3.10 (1H, m), 3.26-3.64 (3H,m), 4.29-5.12 (2H, m), 6.60 (1H, d, J=7.7 Hz), 6.88-7.67 (5H, m),7.92-8.12 (2H, m)

5-Ethoxycarbonylmethoxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 107-108° C. (recrystallized from ethylacetate/n-hexane)

5-(4-Bromobutoxy)-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless oil

¹ H-NMR (CDCl₃) δ: 1.49-2.55 (8H, m), 2.72-3.07 (1H, m), 3.24-3.77 (4H,m), 4.40-5.15 (2H, m), 6.53-6.66 (1H, m), 6.91-7.06 (1H, m), 7.07-7.80(4H, m), 7.94-8.13 (2H, m)

5-(4-Dimethylaminobutoxy)-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless oil

¹ H-NMR (CDCl₃) δ: 1.51-1.88 (6H, m), 2.23-2.61 (4H, m), 2.27 (3H, s),2.35 (3H, s), 2.74-3.14 (1H, m), 3.55-3.77 (2H, m), 4.48-5.11 (2H, m),6.54-6.66 (1H, m), 6.91-7.04 (1H, m), 7.06-7.80 (4H, m), 7.93-8.11 (2H,m)5-[4-(Phthalimid-1-yl)propoxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ: 1.48-2.56 (6H, m), 2.71-3.05 (1H, m), 3.40-4.05 (4H,m), 4.47-5.11 (2H, m), 6.50-6.64 (1H, m), 6.84-7.03 (1H, m), 7.03-7.20(1H, m), 7.20-7.57 (2H, m), 7.57-7.93 (5H, m), 7.97-8.20 (2H, m)

5-Chloro-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, lightbrown powder

¹ H-NMR (CDCl₃) δ: 1.75-3.3 (4H, m), 4.6-6.25 (3H, m), 6.45-6.7 (1H, m),6.8-7.5 (4H, m), 7.55-7.7 (1H, m), 7.9-8.1 (2H, m)

5-Oxo-1-(2-chloro-4-nitorobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,pale yellow amorphous

¹ H-NMR (CDCl₃) δ: 1.95-2.45 (2H, m), 2.94 (1H, t, J=6 Hz), 3.05-5.3(2H, m), 6.96-7.1 (1H, m), 7.12-7.5 (3H, m), 7.75-7.85 (1H, m), 7.95-8.1(1H, m), 8.14 (1H, s)

4-Dimethylaminomethyl-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline,white powder, m.p. 117-119° C.

3-Dimethylamino-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.5-1.7 (1H, m), 2.1-2.4 (1H, m), 2.42 (6H, s),2.6-2.7 (1H, m), 2.8-3.0 (3H, m), 5.1-5.3 (1H, m), 6.62 (1H, d, J=7.8Hz), 6.95 (1H, t, J=7.7 Hz), 7.14 (1H, t, J=7.5 Hz), 7.2-7.4 (3H, m),8.00 (2H, d, J=8.9 Hz)

3-Dimethylamino-1-(3-methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.5-1.7 (1H, m), 2.0-2.3 (1H, m), 2.41 (6H, s),2.5-2.8 (1H, m), 2.8-3.0 (3H, m), 3.75 (3H, s), 5.1-5.3 (1H, m), 6.6-6.8(2H, m), 6.9-7.3 (4H, m), 7.59 (1H, d, J=8.3 Hz)

4-(4-Nitrobenzoyl)-3,4-dihydro-2H-1,4-benzothiazine, yellow powder, m.p.180-182° C.

5-(4-Nitrobenzoyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine, yellowpowder, m.p. 162-163° C.

REFERENCE EXAMPLE 10

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

1-(2-Chloro-4-aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder (recrystallized from methanol/diethyl ether), m.p.194.5-195.5° C.

1-(3-Methyl-4-aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

¹ H-NMR (CDCl₃) δ: 2.01 (3H, s), 2.41 (3H, s), 2.82-3.21 (3H, m),3.50-4.21 (4H, m), 4.78-5.14 (1H, m), 6.24-6.40 (1H, m), 6.59-6.82 (2H,m), 6.90-7.18 (3H, m), 7.19-7.34 (1H, m)

5-Dimethylamino-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from dichloromethane/diethyl ether), m.p.162-164° C.

5-Dimethylamino-1-(2-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(recrystallized from methanol/diethyl ether)

¹ H-NMR (CDCl₃) δ: 1.23-2.80 (11H, m), 2.90-3.38 (1H, m), 3.50-5.19 (6H,m), 5.87-6.41 (2H, m), 6.65-7.56 (5H, m)

5-Methoxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder (recrystallized from ethyl acetate/n-hexane), m.p. 154-155° C.

5-Ethoxycarbonylmethoxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from ethyl acetate/n-hexane), m.p. 231-232°C.

5-(4-Dimethylaminobutoxy)-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless oil

¹ H-NMR (CDCl₃) δ: 1.47-1.83 (6H, m), 1.83-2.54 (4H, m), 2.29 (6H, s),2.61-3.00 (1H, m), 3.36-3.76 (2H, m), 4.35-5.20 (2H, m), 6.27-6.48 (2H,m), 6.57-6.76 (1H, m), 6.90-7.61 (5H, m)

5-[4-(Phthalimid-1-yl)propoxy]-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ: 1.30-2.47 (6H, m), 2.57-3.01 (1H, m), 3.30-4.06 (4H,m), 4.34-5.20 (2H, m), 6.30-6.53 (2H, m), 6.57-6.78 (1H, m), 6.87-7.57(5H, m), 7.62-7.76 (2H, m), 7.76-7.97 (2H, m)

5-Chloro-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, paleyellow amorphous

¹ H-NMR (CDCl₃) δ: 1.35-4.3 (7H, m), 4.55-6.7 (2H, m), 6.3-6.55 (2H, m),6.6-6.8 (1H, m), 6.85-7.45 (5H, m)

5-Oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, pale yellowamorphous

¹ H-NMR (CDCl₃) δ: 1.95-2.35 (2H, m), 2.89 (2H, t, J=6.3 Hz), 3.0-5.3(4H, m), 6.35-6.47 (2H, m), 6.72-6.83 (1H, m), 7.0-7.15 (2H, m),7.18-7.32 (2H, m), 7.81-7.93 (1H, m)

5-Oxo-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder

H-NMR (CDCl₃) δ: 1.85-2.3 (2H, m), 2.87 (2H, t, J=6.2 Hz), 3.1-4.75 (4H,m), 6.15-7.5 (6H, m), 7.65-7.9 (1H, m)

4-Dimethylaminomethyl-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline,white powder, m.p. 123-125° C.

3-Dimethylamino-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 175-177° C.

3-Dimethylamino-1-(3-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.5-1.7 (1H, m), 2.1-2.3 (1H, m), 2.3-2.6 (1H, m),2.40 (6H, s), 2.7-3.0 (3H, m), 3.60 (3H, s), 3.8-4.0 (2H, br), 5.2-5.4(1H, m), 6.37 (1H, d, J=8.2 Hz), 6.5-6.8 (3H, m), 6.9-7.4 (3H, m)

4-(4-Aminobenzoyl)-3,4-dihydro-2H-1,4-benzothiazine, yellow powder, m.p.207-210° C.

5-(4-Aminobenzoyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine, yellowpowder, m.p. 193-195° C.

REFERENCE EXAMPLE 11

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

5-Carbamoyloxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 243-244° C. (recrystallized from ethylacetate/diisopropyl ether)

5-Methylaminocarbonyloxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 207-208° C. (recrystallized from ethylacetate/n-hexane)

5-Dimethylaminocarbonyloxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 155-156° C. (recrystallized from ethylacetate/diisopropyl ether/n-hexane)

5-Methylidenyl-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless prisms, m.p. 133.5-134° C. (recrystallized from ethylacetate/diisopropyl ether)

5-Oxo-6-methyl-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless prisms, m.p. 90-92° C. (recrystallized from ethanol)

1-(4-Nitrobenzoyl)-1,2,3,5-tetrahydro-4,1-benzothiazepine, yellowpowder, m.p. 185-187° C. (recrystallized from dichloromethane/diethylether)

5-Dimethylamino-1-(2-dimethylamino-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder, m.p. 123-125° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine, whitepowder, m.p. 201.5-202.5° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-4-methyl-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder, m.p. 136-138° C. (recrystallized from diethylether/dichloromethane)

5-Dimethylamino-1-(3-methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.16-3.18 (11H, m), 2.18 (3H, s), 3.40-5.15 (2H, m),6.50-7.68 (6H, m), 7.70-7.84 (1H, m)

5-Dimethylamino-1-(2-methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ: 1.19-2.86 (11H, m), 2.20 (3H, s), 2.94-3.24 (1H, m),3.36-5.18 (1H, m), 6.49-8.20 (7H, m)

5-Dimethylamino-1-(2-fluoro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.21-2.66 (10H, m), 2.66-5.11 (3H, m), 6.63-8.25 (7H,m)

5-Dimethylamino-1-(3-fluoro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 152-152.5° C. (recrystallized from chloroform/diethylether)

REFERENCE EXAMPLE 12

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

5-Carbamoyloxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 215-216° C. (recrystallized from ethylacetate/n-hexane)

5-Methylaminocarbonyloxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 192-195° C. (recrystallized from ethylacetate/n-hexane)

5-Dimethylaminocarbonyloxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 228-230° C. (recrystallized from ethylacetate/diisopropyl ether)

5-Methyl-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder, m.p. 155-156° C. (recrystallized from ethyl acetate/n-hexane)

5-Oxo-6-methyl-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 193-195° C. (recrystallized from ethanol)

1-(4-Aminobenzoyl)-1,2,3,5-tetrahydro-4,1-benzothiazepine, white powder,m.p. 179-180° C. (recrystallized from dichloromethane/diethyl ether)

5-Dimethylamino-1-(2-dimethylamino-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 163-165° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, yellowpowder, m.p. 195-197° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-4-methyl-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-1,4-benzazepine,yellow powder, m.p. 190-192° C. (recrystallized from diethylether/dichloromethane)

5-Dimethylamino-1-(2-ethoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 111-114° C. (recrystallized from diethyl ether)

5-Dimethylamino-1-(3-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 0.66-2.56 (14H, m), 2.93-5.22 (4H, m), 6.23-7.80 (7H,m)

5-Dimethylamino-1-(2-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 154-156° C. (recrystallized from methanol/diethylether)

5-Dimethylamino-1-(2-fluoro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 161-163° C. (recrystallized fromdichloromethane/diethyl ether)

5-Dimethylamino-1-(3-fluoro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 156-157° C. (recrystallized from methanol/diethylether)

5-Oxo-1-(2-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless prisms, m.p. 160-160.5° C. (recrystallized frommethanol/diethyl ether)

EXAMPLE 1

To a solution of 1,2,3,4-tetrahydroquinoline (28.7 g) in acetone (400ml) and water (200 ml) is added potassium carbonate (38.8 g) and furtherthereto is added 4-benzoylaminobenzoyl chloride (56 g) underice-cooling. The mixture is stirred at room temperature overnight. Wateris added to the reaction mixture, and the mixture is extracted withdichloromethane. The extract is dried over magnesium sulfate, and thesolvent is distilled off under reduced pressure. The resulting residueis purified by silica gel column chromatography and recrystallized frommethanol to give1-[4-(benzoylamino)benzoyl-]-1,2,3,4-tetrahydroquinoline (57 g) as whitepowder, m.p. 202.5-203.5° C.

Using the suitable starting materials, the compounds as shown in thefollowing Table 1 are obtained in the same manner as in Example 1.

                  TABLE 1                                                         ______________________________________                                        1 #STR87##                                                                    ______________________________________                                        Example 2                                                                       Structure                                                                      -                                                                          2  STR88##                                                                       -                                                                          3  STR89##                                                                       - Crystalline form: Light yellow powder                                      Recrystallization solvent: Methanol                                           Melting Point: 198.5-199.5° C.                                         Form: Free                                                                    Example 3                                                                     Structure                                                                      -                                                                          2 -  - 0##                                                                    4  STR91##                                                                       - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 200.5-201.5° C.                                         Form: Free                                                                    Example 4                                                                     Structure                                                                      -                                                                          2  STR92##                                                                       -                                                                          5  STR93##                                                                      Crystalline form: Yellow powder                                               Recrystallization solvent: Methanol                                           Melting Point: 206-207° C.                                             Form: Free                                                                    Example 5                                                                     Structure                                                                      -                                                                          2  STR94##                                                                       -                                                                          6  STR95##                                                                       - Crystalline form: Yellow powder                                            Recrystallization solvent: Methanol                                           Melting Point: 216-217° C.                                             Form: Free                                                                    Example 6                                                                     Structure                                                                      -                                                                          2  STR96##                                                                       -                                                                          7  STR97##                                                                       - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 202-203° C.                                             Form: Free                                                                    Example 7                                                                     Structure                                                                      -                                                                          2  STR98##                                                                       -                                                                          8  STR99##                                                                       - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 212-213° C.                                             Form: Free                                                                    Example 8                                                                     Structure                                                                      -                                                                          2  STR100##                                                                      -                                                                          9  STR101##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 167.5-168.5° C.                                         Form: Free                                                                    Example 9                                                                     Structure                                                                      -                                                                          2  STR102##                                                                      -                                                                          0  STR103##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 205-206° C.                                             Form: Free                                                                    Example 10                                                                    Structure                                                                      -                                                                          2  STR104##                                                                      -                                                                          1  STR105##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: >300° C.                                                NMR analysis: 1)                                                              Form: Free                                                                    Example 11                                                                    Structure                                                                      -                                                                          2  STR106##                                                                      -                                                                          2  STR107##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Methanol                                           Melting Point: 176-177° C.                                             Form: Free                                                                    Example 12                                                                    Structure                                                                      -                                                                          2  STR108##                                                                      -                                                                          3  STR109##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 219-220° C.                                             Form: Free                                                                    Example 13                                                                    Structure                                                                      -                                                                          2  STR110##                                                                      -                                                                          4  STR111##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 193-194° C.                                             Form: Free                                                                    Example 14                                                                    Structure                                                                      -                                                                          2  STR112##                                                                      -                                                                          5  STR113##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 232-233° C.                                             Form: Free                                                                    Example 15                                                                    Structure                                                                      -                                                                          2  STR114##                                                                      -                                                                          6  STR115##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 209-210° C.                                             Form: Free                                                                    Example 16                                                                    Structure                                                                      -                                                                          2  STR116##                                                                      -                                                                          7  STR117##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 184.5-185.5° C.                                         Form: Free                                                                    Example 17                                                                    Structure                                                                      -                                                                          2  STR118##                                                                      -                                                                          8  STR119##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 224.5-225.5° C.                                         Form: Free                                                                    Example 18                                                                    Structure                                                                      -                                                                          2  STR120##                                                                      -                                                                          9  STR121##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 220.5-221.5° C.                                         Form: Free                                                                    Example 19                                                                    Structure                                                                      -                                                                          2  STR122##                                                                      -                                                                          0  STR123##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Methanol                                           Melting Point: 231-232° C.                                             Form: Free                                                                    Example 20                                                                    Structure                                                                      -                                                                          2  STR124##                                                                      -                                                                          1  STR125##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: >300° C.                                                NMR analysis: 2)                                                              Form: Free                                                                    Example 21                                                                    Structure                                                                      -                                                                          2  STR126##                                                                      -                                                                          2  STR127##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 208-209° C.                                             Form: Free                                                                    Example 22                                                                    Structure                                                                      -                                                                          2  STR128##                                                                      -                                                                          3  STR129##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 234.5-235.5° C.                                         Form: Free                                                                    Example 23                                                                    Structure                                                                      -                                                                          2  STR130##                                                                      -                                                                          4  STR131##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Methanol                                           Melting Point: 263.5-264.5° C.                                         Form: Free                                                                    Example 24                                                                    Structure                                                                      -                                                                          2  STR132##                                                                      -                                                                          5  STR133##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 237-238° C.                                             Form: Free                                                                    Example 25                                                                    Structure                                                                      -                                                                          2  STR134##                                                                      -                                                                          6  STR135##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 234-235° C.                                             Form: Free                                                                    Example 26                                                                    Structure                                                                      -                                                                          2  STR136##                                                                      -                                                                          7  STR137##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 236.5-237.5° C.                                         Form: Free                                                                    Example 27                                                                    Structure                                                                      -                                                                          2  STR138##                                                                      -                                                                          8  STR139##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 206.5-207.5° C.                                         Form: Free                                                                    Example 28                                                                    Structure                                                                      -                                                                          2  STR140##                                                                      -                                                                          9  STR141##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 210-211° C.                                             Form: Free                                                                    Example 29                                                                    Structure                                                                      -                                                                          2  STR142##                                                                      -                                                                          0  STR143##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 210.5-211.5° C.                                         Form: Free                                                                    Example 30                                                                    Structure                                                                      -                                                                          2  STR144##                                                                      -                                                                          1  STR145##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 178-179° C.                                             Form: Free                                                                    Example 31                                                                    Structure                                                                      -                                                                          2  STR146##                                                                      -                                                                          2  STR147##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 192-193° C.                                             Form: Free                                                                    Example 32                                                                    Structure                                                                      -                                                                          2  STR148##                                                                      -                                                                          3  STR149##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 217-218° C.                                             Form: Free                                                                    Example 33                                                                    Structure                                                                      -                                                                          2  STR150##                                                                      -                                                                          4  STR151##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 143-144° C.                                             Form: Free                                                                    Example 34                                                                    Structure                                                                      -                                                                          2  STR152##                                                                      -                                                                          5  STR153##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 170.5-171.5° C.                                         Form: Free                                                                    Example 35                                                                    Structure                                                                      -                                                                          2  STR154##                                                                      -                                                                          6  STR155##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 169.5-170.5° C.                                         Form: Free                                                                    Example 36                                                                    Structure                                                                      -                                                                          2  STR156##                                                                      -                                                                          7  STR157##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 174.5-175.5° C.                                         Form: Free                                                                    Example 37                                                                    Structure                                                                      -                                                                          2  STR158##                                                                      -                                                                          8  STR159##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 148.5-149.5° C.                                         Form: Free                                                                    Example 38                                                                    Structure                                                                      -                                                                          2  STR160##                                                                      -                                                                          9  STR161##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 165-166° C.                                             Form: Free                                                                    Example 39                                                                    Structure                                                                      -                                                                          2  STR162##                                                                      -                                                                          0  STR163##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 243-244° C.                                             Form: Free                                                                    Example 40                                                                    Structure                                                                      -                                                                          2  STR164##                                                                      -                                                                          1  STR165##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 199-200° C.                                             Form: Free                                                                    Example 41                                                                    Structure                                                                      -                                                                          2  STR166##                                                                      -                                                                          2  STR167##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 232.5-233.5° C.                                         Form: Free                                                                    Example 42                                                                    Structure                                                                      -                                                                          2  STR168##                                                                      -                                                                          3  STR169##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 178.5-179.5° C.                                         Form: Free                                                                    Example 43                                                                    Structure                                                                      -                                                                          2  STR170##                                                                      -                                                                          4  STR171##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting point: 205.5-206.5° C.                                         Form: Free                                                                    Example 44                                                                    Structure                                                                      -                                                                          2  STR172##                                                                      -                                                                          5  STR173##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 234-235° C.                                             Form: Free                                                                    Example 45                                                                    Structure                                                                      -                                                                          2  STR174##                                                                      -                                                                          6  STR175##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 225-226° C.                                             Form: Free                                                                    Example 46                                                                    Structure                                                                      -                                                                          2  STR176##                                                                      -                                                                          7  STR177##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 224-225° C.                                             Form: Free                                                                    Example 47                                                                    Structure                                                                      -                                                                          2  STR178##                                                                      -                                                                          8  STR179##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 236-237° C.                                             Form: Free                                                                    Example 48                                                                    Structure                                                                      -                                                                          2  STR180##                                                                      -                                                                          9  STR181##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Methanol                                           Melting Point: 175.5-176.5° C.                                         Form: Free                                                                    Example 49                                                                    Structure                                                                      -                                                                          2  STR182##                                                                      -                                                                          0  STR183##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 231-232° C.                                             Form: Free                                                                    Example 50                                                                    Structure                                                                      -                                                                          2  STR184##                                                                      -                                                                          1  STR185##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Methanol                                           Melting Point: 204-205° C.                                             Form: Free                                                                    Example 51                                                                    Structure                                                                      -                                                                          2  STR186##                                                                      -                                                                          2  STR187##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting point: 190-191° C.                                             Form: Free                                                                    Example 52                                                                    Structure                                                                      -                                                                          2  STR188##                                                                      -                                                                          3  STR189##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting point: 156-157° C.                                             Form: Free                                                                    Example 53                                                                    Structure                                                                      -                                                                          2  STR190##                                                                      -                                                                          4  STR191##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 200-201° C.                                             Form: Free                                                                    Example 54                                                                    Structure                                                                      -                                                                          2  STR192##                                                                      -                                                                          5  STR193##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 206-207° C.                                             Form: Free                                                                    Example 55                                                                    Structure                                                                      -                                                                          2  STR194##                                                                      -                                                                          6  STR195##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 3)                                                              Form: Free                                                                    Example 56                                                                    Structure                                                                      -                                                                          2  STR196##                                                                      -                                                                          7  STR197##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting point: 215.5-216.5° C.                                         Form: Free                                                                    Example 57                                                                    Structure                                                                      -                                                                          2  STR198##                                                                      -                                                                          8  STR199##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 189-190° C.                                             Form: Free                                                                    Example 58                                                                    Structure                                                                      -                                                                          2  STR200##                                                                      -                                                                          9  STR201##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 203.5-204.5° C.                                         Form: Free                                                                    Example 59                                                                    Structure                                                                      -                                                                          2  STR202##                                                                      -                                                                          0  STR203##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Methanol                                           Melting Point: 254.5-255.5° C.                                         Form: Free                                                                    Example 60                                                                    Structure                                                                      -                                                                          2  STR204##                                                                      -                                                                          1  STR205##                                                                      - Crystalline form: Brown powder                                             Recrystallization solvent: Methanol                                           Melting Point: 182.5-183.5° C.                                         Form: Free                                                                    Example 61                                                                    Structure                                                                      -                                                                          2  STR206##                                                                      -                                                                          2  STR207##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 4)                                                              Form: Free                                                                    Example 62                                                                    Structure                                                                      -                                                                          2  STR208##                                                                      -                                                                          3  STR209##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 263-264° C.                                             Form: Free                                                                    Example 63                                                                    Structure                                                                      -                                                                          2  STR210##                                                                      -                                                                          4  STR211##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 217-218° C.                                             Form: Free                                                                    Example 64                                                                    Structure                                                                      -                                                                          2  STR212##                                                                      -                                                                          5  STR213##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 183-184° C.                                             Form: Free                                                                    Example 65                                                                    Structure                                                                      -                                                                          2  STR214##                                                                      -                                                                          6  STR215##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 207.5-208.5° C.                                         Form: Free                                                                    Example 66                                                                    Structure                                                                      -                                                                          2  STR216##                                                                      -                                                                          7  STR217##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 251-252° C.                                             Form: Free                                                                    Example 67                                                                    Structure                                                                      -                                                                          2  STR218##                                                                      -                                                                          8  STR219##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 208.5-209.5° C.                                         Form: Free                                                                    Example 68                                                                    Structure                                                                      -                                                                          2  STR220##                                                                      -                                                                          9  STR221##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 231-232° C.                                             Form: Free                                                                    Example 69                                                                    Structure                                                                      -                                                                          2  STR222##                                                                      -                                                                          0  STR223##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 5)                                                              Form: Free                                                                    Example 70                                                                    Structure                                                                      -                                                                          2  STR224##                                                                      -                                                                          1  STR225##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 134-135° C.                                             Form: Free                                                                    Example 71                                                                    Structure                                                                      -                                                                          2  STR226##                                                                      -                                                                          2  STR227##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Methanol                                           Melting point: 115-116° C.                                             Form: Free                                                                    Example 72                                                                    Structure                                                                      -                                                                          2  STR228##                                                                      -                                                                          3  STR229##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 178.5-179.5° C.                                         Form: Free                                                                    Example 73                                                                    Structure                                                                      -                                                                          2  STR230##                                                                      -                                                                          4  STR231##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 182.5-183.5° C.                                         Form: Free                                                                    Example 74                                                                    Structure                                                                      -                                                                          2  STR232##                                                                      -                                                                          5  STR233##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 164-165° C.                                             Form: Free                                                                    Example 75                                                                    Structure                                                                      -                                                                          2  STR234##                                                                      -                                                                          6  STR235##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 6)                                                              Form: Free                                                                    Example 76                                                                    Structure                                                                      -                                                                          2  STR236##                                                                      -                                                                          7  STR237##                                                                      - Crystalline form: Yellow amorphous                                         NMR analysis: 7)                                                              Form: Free                                                                    Example 77                                                                    Structure                                                                      -                                                                          2  STR238##                                                                      -                                                                          8  STR239##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 155-156° C.                                             Form: Free                                                                    Example 78                                                                    Structure                                                                      -                                                                          2  STR240##                                                                      -                                                                          9  STR241##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 182.5-183. 5° C.                                        Form: Free                                                                    Example 79                                                                    Structure                                                                      -                                                                          2  STR242##                                                                      -                                                                          0  STR243##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 164.5-165.5° C.                                         Form: Free                                                                    Example 80                                                                    Structure                                                                      -                                                                          2  STR244##                                                                      -                                                                          1  STR245##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 165-167° C.                                             Form: Free                                                                    Example 81                                                                    Structure                                                                      -                                                                          2  STR246##                                                                      -                                                                          2  STR247##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 124-125° C.                                             Form: Free                                                                    Example 82                                                                    Structure                                                                      -                                                                          2  STR248##                                                                      -                                                                          3  STR249##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 140.5-141.5° C.                                         Form: Free                                                                    Example 83                                                                    Structure                                                                      -                                                                          2  STR250##                                                                      -                                                                          4  STR251##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 8)                                                              Form: Free                                                                    Example 84                                                                    Structure                                                                      -                                                                          2  STR252##                                                                      -                                                                          5  STR253##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 211-212° C.                                             Form: Free                                                                    Example 85                                                                    Structure                                                                      -                                                                          2  STR254##                                                                      -                                                                          6  STR255##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 178-179° C.                                             Form: Free                                                                    Example 86                                                                    Structure                                                                      -                                                                          2  STR256##                                                                      -                                                                          7  STR257##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 212.5-213.5° C.                                         Form: Free                                                                    Example 87                                                                    Structure                                                                      -                                                                          2  STR258##                                                                      -                                                                          8  STR259##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 193-194° C.                                             Form: Free                                                                    Example 88                                                                    Structure                                                                      -                                                                          2  STR260##                                                                      -                                                                          9  STR261##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 203-204° C.                                             Form: Free                                                                    Example 89                                                                    Structure                                                                      -                                                                          2  STR262##                                                                      -                                                                          0  STR263##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 9)                                                              Form: Free                                                                    Example 90                                                                    Structure                                                                      -                                                                          2  STR264##                                                                      -                                                                          1  STR265##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 10)                                                             Form: Free                                                                    Example 91                                                                    Structure                                                                      -                                                                          2  STR266##                                                                      -                                                                          2  STR267##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 11)                                                             Form: Free                                                                    Example 92                                                                    Structure                                                                      -                                                                          2  STR268##                                                                      -                                                                          3  STR269##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 156.5-157.5° C.                                         Form: Free                                                                    Example 93                                                                    Structure                                                                      -                                                                          2  STR270##                                                                      -                                                                          4  STR271##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 12)                                                             Form: Free                                                                    Example 94                                                                    Structure                                                                      -                                                                          2  STR272##                                                                      -                                                                          5  STR273##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 203.5-204.5° C.                                         Form: Free                                                                    Example 95                                                                    Structure                                                                      -                                                                          2  STR274##                                                                      -                                                                          6  STR275##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 13)                                                             Form: Free                                                                    Example 96                                                                    Structure                                                                      -                                                                          2  STR276##                                                                      -                                                                          7  STR277##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Methanol                                           Melting Point: 126-127° C.                                             Form: Free                                                                    Example 97                                                                    Structure                                                                      -                                                                          2  STR278##                                                                      -                                                                          8  STR279##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 158.5-159.5° C.                                         Form: Free                                                                    Example 98                                                                    Structure                                                                      -                                                                          2  STR280##                                                                      -                                                                          9  STR281##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 129-130° C.                                             Form: Free                                                                    Example 99                                                                    Structure                                                                      -                                                                          2  STR282##                                                                      -                                                                          0  STR283##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 131.5-132.5° C.                                         Form: Free                                                                    Example 100                                                                   Structure                                                                      -                                                                          2  STR284##                                                                      -                                                                          1  STR285##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 140-141° C.                                             Form: Free                                                                    Example 101                                                                   Structure                                                                      -                                                                          2  STR286##                                                                      -                                                                          2  STR287##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Meltinq Point: 138.5-139.5° C.                                         Form: Free                                                                    Example 102                                                                   Structure                                                                      -                                                                          2  STR288##                                                                      -                                                                          3  STR289##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 128-129° C.                                             Form: Free                                                                    Example 103                                                                   Structure                                                                      -                                                                          2  STR290##                                                                      -                                                                          4  STR291##                                                                      - Crystalline form: White powder                                             Recrystaliization solvent: Methanol                                           Melting Point: 160-161° C.                                             Form: Free                                                                    Example 104                                                                   Structure                                                                      -                                                                          5  STR292##                                                                      -                                                                          1  STR293##                                                                      - Crystalline form: White powder                                             Recrystaliization solvent: Methanol                                           Melting Point: 175-176° C.                                             Form: Free                                                                    Example 105                                                                   Structure                                                                   5  STR294##                                                                      -                                                                          7  STR295##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 197-198° C.                                             Form: Free                                                                    Example 106                                                                   Structure                                                                   5  STR296##                                                                      -                                                                          8  STR297##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 204-2O0° C.                                             Form: Free                                                                    Example 107                                                                   Structure                                                                      -                                                                          5  STR298##                                                                      -                                                                          9  STR299##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 174-175° C.                                             Form: Free                                                                    Example 108                                                                   Structure                                                                      -                                                                          5  STR300##                                                                      -                                                                          0  STR301##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Methanol                                           Melting Point: 202-203° C.                                             Form: Free                                                                    Example 109                                                                   Structure                                                                      -                                                                          5  STR302##                                                                      -                                                                          1  STR303##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 203-204° C.                                             Form: Free                                                                    Example 110                                                                   Structure                                                                      -                                                                          5  STR304##                                                                      -                                                                          2  STR305##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 170.5-171.5° C.                                         Form: Free                                                                    Example 111                                                                   Structure                                                                      -                                                                          5  STR306##                                                                      -                                                                          3  STR307##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 149-150° C.                                             Form: Free                                                                    Example 112                                                                   Structure                                                                      -                                                                          5  STR308##                                                                      -                                                                          4  STR309##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 185-186° C.                                             Form: Free                                                                    Example 113                                                                   Structure                                                                      -                                                                          5  STR310##                                                                      -                                                                          5  STR311##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethanoi                            Melting Point: 225-226° C.                                             Form: Free                                                                    Example 114                                                                   Structure                                                                      -                                                                          6  STR312##                                                                      -                                                                          7  STR313##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 234-235° C.                                             Form: Free                                                                    Example 115                                                                   Structure                                                                      -                                                                          6  STR314##                                                                      -                                                                          8  STR315##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 149.5-150.5° C.                                         Form: Free                                                                    Example 116                                                                   Structure                                                                      -                                                                          6  STR316##                                                                      -                                                                          9  STR317##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 197-198° C.                                             Form: Free                                                                    Example 117                                                                   Structure                                                                      -                                                                          0  STR318##                                                                      -                                                                          1  STR319##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 204-205° C.                                             Form: Free                                                                    Example 118                                                                   Structure                                                                      -                                                                          0  STR320##                                                                      -                                                                          2  STR321##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 224.5-225.5° C.                                         Form: Free                                                                    Example 119                                                                   Structure                                                                      -                                                                          0  STR322##                                                                      -                                                                          3  STR323##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 189.5-190.5° C.                                         Form: Free                                                                    Example 120                                                                   Structure                                                                      -                                                                          2  STR324##                                                                      -                                                                          4  STR325##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 221.5-222.5° C.                                         Form: Free                                                                    Example 121                                                                   Structure                                                                      -                                                                          2  STR326##                                                                      -                                                                          5  STR327##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Methanol                                           Melting Point: 154-155° C.                                             Form: Free                                                                    Example 122                                                                   Structure                                                                      -                                                                          2  STR328##                                                                      -                                                                          6  STR329##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 165-166° C.                                             Form: Free                                                                    Example 123                                                                   Structure                                                                      -                                                                          2  STR330##                                                                      -                                                                          7  STR331##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Methanol                                           Melting Point: 141-142° C.                                             Form: Free                                                                    Example 124                                                                   Structure                                                                      -                                                                          2  STR332##                                                                      -                                                                          8  STR333##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 165.5-166.5° C.                                         Form: Free                                                                    Example 125                                                                   Structure                                                                      -                                                                          2  STR334##                                                                      -                                                                          9  STR335##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Methanol                                           Melting point: 164-165° C.                                             Form: Free                                                                    Example 126                                                                   Structure                                                                      -                                                                          2  STR336##                                                                      -                                                                          0  STR337##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 203.5-204.5° C.                                         Form: Free                                                                    Example 127                                                                   Structure                                                                      -                                                                          2  STR338##                                                                      -                                                                          1  STR339##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 236.5-237.5° C.                                         Form: Free                                                                    Example 128                                                                   Structure                                                                      -                                                                          2  STR340##                                                                      -                                                                          2  STR341##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 206.5-207.5° C.                                         Form: Free                                                                    Example 129                                                                   Structure                                                                      -                                                                          2  STR342##                                                                      -                                                                          3  STR343##                                                                      - Crystalline form : White powder                                            Recrystallization solvent: Methanol                                           Melting Point: 271-272° C.                                             Form: Free                                                                    Example 130                                                                   Structure                                                                      -                                                                          2  STR344##                                                                      -                                                                          4  STR345##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Meiting Point: 246-247° C.                                             Form: Free                                                                    Example 131                                                                   Structure                                                                      -                                                                          5  STR346##                                                                      -                                                                          6  STR347##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 210-211° C.                                             Form: Free                                                                    Example 132                                                                   Structure                                                                      -                                                                          5  STR348##                                                                      -                                                                          7  STR349##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 230.5-231.5° C.                                         Form: Free                                                                    Example 133                                                                   Structure                                                                      -                                                                          5  STR350##                                                                      -                                                                          8  STR351##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 203-204° C.                                             Form: Free                                                                    Example 134                                                                   Structure                                                                      -                                                                          5  STR352##                                                                      -                                                                          9  STR353##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 170-171° C.                                             Form: Free                                                                    Example 135                                                                   Structure                                                                      -                                                                          5  STR354##                                                                      -                                                                          0  STR355##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 225.5-226.5° C.                                         Form: Free                                                                    Example 136                                                                   Structure                                                                      -                                                                          5  STR356##                                                                      -                                                                          1  STR357##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 210.5-211.5° C.                                         Form: Free                                                                    Example 137                                                                   Structure                                                                      -                                                                          5  STR358##                                                                      -                                                                          2  STR359##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 183-184° C.                                             Form: Free                                                                    Example 138                                                                   Structure                                                                      -                                                                          5  STR360##                                                                      -                                                                          3  STR361##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 191.5-192.5° C.                                         Form: Free                                                                    Example 139                                                                   Structure                                                                      -                                                                          5  STR362##                                                                      -                                                                          4  STR363##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 203.5-204.5° C.                                         Form: Free                                                                    Example 140                                                                   Structure                                                                      -                                                                          5  STR364##                                                                      -                                                                          5  STR365##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 215.5-216.5° C.                                         Form: Free                                                                    Example 141                                                                   Structure                                                                      -                                                                          5  STR366##                                                                      -                                                                          6  STR367##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 211.5-212.5° C.                                         Form: Free                                                                    Example 142                                                                   Structure                                                                      -                                                                          5  STR368##                                                                      -                                                                          7  STR369##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 280.5-281.5° C.                                         Form: Free                                                                    Example 143                                                                   Structure                                                                      -                                                                          5  STR370##                                                                      -                                                                          8  STR371##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 235.5-236.5° C.                                         Form: Free                                                                    Example 144                                                                   Structure                                                                      -                                                                          5  STR372##                                                                      -                                                                          9  STR373##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/dichloromethane                            Melting Point: 249.5-250.5° C.                                         Form: Free                                                                    Example 145                                                                   Structure                                                                      -                                                                          5  STR374##                                                                      -                                                                          0  STR375##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 217-218° C.                                             Form: Free                                                                    Example 146                                                                   Structure                                                                      -                                                                          5  STR376##                                                                      -                                                                          1  STR377##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 201.5-203° C.                                           Form: Free                                                                    Example 147                                                                   Structure                                                                      -                                                                          7  STR378##                                                                      -                                                                          2  STR379##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 221-222° C.                                             Form: Free                                                                    Example 148                                                                   Structure                                                                      -                                                                          7  STR380##                                                                      -                                                                          3  STR381##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 193-194° C.                                             Form: Free                                                                    Example 149                                                                   Structure                                                                      -                                                                          7  STR382##                                                                      -                                                                          4  STR383##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 176-177° C.                                             Form: Free                                                                    Example 150                                                                   Structure                                                                      -                                                                          7  STR384##                                                                      -                                                                          5  STR385##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 188-189.5° C.                                           Form: Free                                                                    Example 151                                                                   Structure                                                                      -                                                                          7  STR386##                                                                      -                                                                          6  STR387##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 227-228° C.                                             Form: Free                                                                    Example 152                                                                   Structure                                                                      -                                                                          7  STR388##                                                                      -                                                                          7  STR389##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 186-187° C.                                             Form: Free                                                                    Example 153                                                                   Structure                                                                      -                                                                          0  STR390##                                                                      -                                                                          8  STR391##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 135-136° C.                                             Form: Free                                                                    Example 154                                                                   Structure                                                                      -                                                                          0  STR392##                                                                      -                                                                          9  STR393##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 173-174° C.                                             Form: Free                                                                    Example 155                                                                   Structure                                                                      -                                                                          0  STR394##                                                                      -                                                                          0  STR395##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 174.5-175.5° C.                                         Form: Free                                                                    Example 156                                                                   Structure                                                                      -                                                                          0  STR396##                                                                      -                                                                          1  STR397##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 156-157° C.                                             Form: Free                                                                    Example 157                                                                   Structure                                                                      -                                                                          0  STR398##                                                                      -                                                                          2  STR399##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 153-154° C.                                             Form: Free                                                                    Example 158                                                                   Structure                                                                      -                                                                          0  STR400##                                                                      -                                                                          3  STR401##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 169-170° C.                                             Form: Free                                                                    Example 159                                                                   Structure                                                                      -                                                                          0  STR402##                                                                      -                                                                          3  STR403##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 185-186° C.                                             Form: Free                                                                    Example 160                                                                   Structure                                                                      -                                                                          4  STR404##                                                                      -                                                                          5  STR405##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 213-214° C.                                             Form: Free                                                                    Example 161                                                                   Structure                                                                      -                                                                          4  STR406##                                                                      -                                                                          6  STR407##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 240-241° C.                                             Form: Free                                                                    Example 162                                                                   Structure                                                                      -                                                                          4  STR408##                                                                      -                                                                          7  STR409##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 225-226° C.                                             Form: Free                                                                    Example 163                                                                   Structure                                                                      -                                                                          4  STR410##                                                                      -                                                                          8  STR411##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 209.5-210.5° C.                                         Form: Free                                                                    Example 164                                                                   Structure                                                                      -                                                                          4  STR412##                                                                      -                                                                          9  STR413##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 198-199° C.                                             Form: Free                                                                    Example 165                                                                   Structure                                                                      -                                                                          4  STR414##                                                                      -                                                                          0  STR415##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 214.5-215.5° C.                                         Form: Free                                                                    Example 166                                                                   Structure                                                                      -                                                                          4  STR416##                                                                      -                                                                          1  STR417##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 196.5-197.5° C.                                         Form: Free                                                                    Example 167                                                                   Structure                                                                      -                                                                          4  STR418##                                                                      -                                                                          2  STR419##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 194-195° C.                                             Form: Free                                                                    Example 168                                                                   Structure                                                                      -                                                                          4  STR420##                                                                      -                                                                          3  STR421##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 191-192° C.                                             Form: Free                                                                    Example 169                                                                   Structure                                                                      -                                                                          4  STR422##                                                                      -                                                                          5  STR423##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 227-228° C.                                             Form: Free                                                                    Example 170                                                                   Structure                                                                      -                                                                          4  STR424##                                                                      -                                                                          1  STR425##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 182-183° C.                                             Form: Free                                                                    Example 171                                                                   Structure                                                                      -                                                                          4  STR426##                                                                      -                                                                          7  STR427##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 222-223° C.                                             Form: Free                                                                    Example 172                                                                   Structure                                                                      -                                                                          4  STR428##                                                                      -                                                                          8  STR429##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 204-205° C.                                             Form: Free                                                                    Example 173                                                                   Structure                                                                      -                                                                          4  STR430##                                                                      -                                                                          9  STR431##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 194-195° C.                                             Form: Free                                                                    Example 174                                                                   Structure                                                                      -                                                                          4  STR432##                                                                      -                                                                          0  STR433##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 213-214° C.                                             Form: Free                                                                    Example 175                                                                   Structure                                                                      -                                                                          4  STR434##                                                                      -                                                                          1  STR435##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 201-202° C.                                             Form: Free                                                                    Example 176                                                                   Structure                                                                      -                                                                          4  STR436##                                                                      -                                                                          2  STR437##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 173-174° C.                                             Form: Free                                                                    Example 177                                                                   Structure                                                                      -                                                                          4  STR438##                                                                      -                                                                          3  STR439##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 150.5-151.5° C.                                         Form: Free                                                                    Example 178                                                                   Structure                                                                      -                                                                          4  STR440##                                                                      -                                                                          0  STR441##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 207.5-208.5° C.                                         Form: Free                                                                    Example 179                                                                   Structure                                                                      -                                                                          4  STR442##                                                                      -                                                                          6  STR443##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 256.5-257.5° C.                                         Form: Free                                                                    Example 180                                                                   Structure                                                                      -                                                                          5  STR444##                                                                      -                                                                          1  STR445##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 199.5-200.5° C.                                         Form: Free                                                                    Example 181                                                                   Structure                                                                      -                                                                          5  STR446##                                                                      -                                                                          9  STR447##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 211-212° C.                                             Form: Free                                                                    Example 182                                                                   Structure                                                                      -                                                                          5  STR448##                                                                      -                                                                          0  STR449##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 189.5-190.5° C.                                         Form: Free                                                                    Example 183                                                                   Structure                                                                      -                                                                          5  STR450##                                                                      -                                                                          9  STR451##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 176.5-177.5° C.                                         Form: Free                                                                    Example 184                                                                   Structure                                                                      -                                                                          5  STR452##                                                                      -                                                                          0  STR453##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 202-203° C.                                             Form: Free                                                                    Example 185                                                                   Structure                                                                      -                                                                          5  STR454##                                                                      -                                                                          0  STR455##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 219-220° C.                                             Form: Free                                                                    Example 186                                                                   Structure                                                                      -                                                                          5  STR456##                                                                      -                                                                          6  STR457##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 272-273° C.                                             Form: Free                                                                    Example 187                                                                   Structure                                                                      -                                                                          6  STR458##                                                                      -                                                                          1  STR459##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 146-147° C.                                             Form: Free                                                                    Example 188                                                                   Structure                                                                      -                                                                          6  STR460##                                                                      -                                                                          9  STR461##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 229.5-230.5° C.                                         Form: Free                                                                    Example 189                                                                   Structure                                                                      -                                                                          6  STR462##                                                                      -                                                                          7  STR463##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 119.5-120.5° C.                                         Form: Free                                                                    Example 190                                                                   Structure                                                                      -                                                                          6  STR464##                                                                      -                                                                          8  STR465##                                                                      - Crystalline form: Yelllow powder                                           Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 189-190° C.                                             Form: Free                                                                    Example 191                                                                   Structure                                                                      -                                                                          6  STR466##                                                                      -                                                                          9  STR467##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 207-208° C.                                             Form: Free                                                                    Example 192                                                                   Structure                                                                      -                                                                          6  STR468##                                                                      -                                                                          0  STR469##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 196.5-197.5° C.                                         Form: Free                                                                    Example 193                                                                   Structure                                                                      -                                                                          6  STR470##                                                                      -                                                                          1  STR471##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 182-183° C.                                             Form: Free                                                                    Example 194                                                                   Structure                                                                      -                                                                          6  STR472##                                                                      -                                                                          2  STR473##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 172-173° C.                                             Form: Free                                                                    Example 195                                                                   Structure                                                                      -                                                                          6  STR474##                                                                      -                                                                          0  STR475##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 197.5-198.5° C.                                         Form: Free                                                                    Example 196                                                                   Structure                                                                      -                                                                          6  STR476##                                                                      -                                                                          6  STR477##                                                                      - Crystalline form: Yellow powder                                            Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 227-228° C.                                             Form: Free                                                                    Example 197                                                                   Structure                                                                      -                                                                          7  STR478##                                                                      -                                                                          9  STR479##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 216.5-217.5° C.                                         Form: Free                                                                    Example 198                                                                   Structure                                                                      -                                                                          7  STR480##                                                                      -                                                                          1  STR481##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 207-208° C.                                             Form: Free                                                                    Example 199                                                                   Structure                                                                      -                                                                          7  STR482##                                                                      -                                                                          6  STR483##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 236-237° C.                                             Form: Free                                                                    Example 200                                                                   Structure                                                                      -                                                                          7  STR484##                                                                      -                                                                          7  STR485##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 199.5-200.5° C.                                         Form: Free                                                                    Example 201                                                                   Structure                                                                      -                                                                          7  STR486##                                                                      -                                                                          8  STR487##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 171.5-172.5° C.                                         Form: Free                                                                    Example 202                                                                   Structure                                                                      -                                                                          7  STR488##                                                                      -                                                                          9  STR489##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 222.5-223.5° C.                                         Form: Free                                                                    Example 203                                                                   Structure                                                                      -                                                                          7  STR490##                                                                      -                                                                          0  STR491##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 209.5-210.5° C.                                         Form: Free                                                                    Example 204                                                                   Structure                                                                      -                                                                          9  STR492##                                                                      -                                                                          1  STR493##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 14)                                                             Form: Hydrochloride                                                           Example 205                                                                   Structure                                                                      -                                                                          9  STR494##                                                                      -                                                                          6  STR495##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 15)                                                             Form: Hydrochloride                                                           Example 206                                                                   Structure                                                                      -                                                                          9  STR496##                                                                      -                                                                          0  STR497##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 16)                                                             Form: Hydrochloride                                                           Example 207                                                                   Structure                                                                      -                                                                          9  STR498##                                                                      -                                                                          9  STR499##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 17)                                                             Form: Hydrochloride                                                           Example 208                                                                   Structure                                                                      -                                                                          9  STR500##                                                                      -                                                                          8  STR501##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 18)                                                             Form: Hydrochloride                                                           Example 209                                                                   Structure                                                                      -                                                                          9  STR502##                                                                      -                                                                          7  STR503##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 19)                                                             Form: Hydrochloride                                                           Example 210                                                                   Structure                                                                      -                                                                          9  STR504##                                                                      -                                                                          0  STR505##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 20)                                                             Form: Hydrochloride                                                           Example 211                                                                   Structure                                                                      -                                                                          9  STR506##                                                                      -                                                                          0  STR507##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 159.5-1600.5° C.                                        Form: Free                                                                    Example 212                                                                   Structure                                                                      -                                                                          9  STR508##                                                                      -                                                                          2  STR509##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 189.5-190.5° C.                                         Form: Free                                                                    Example 213                                                                   Structure                                                                      -                                                                          9  STR510##                                                                      -                                                                          9  STR511##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 170.5-171.5° C.                                         Form: Free                                                                    Example 214                                                                   Structure                                                                      -                                                                          9  STR512##                                                                      -                                                                          1  STR513##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 165-166° C.                                             Form: Free                                                                    Example 215                                                                   Structure                                                                      -                                                                          9  STR514##                                                                      -                                                                          1  STR515##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 173.5-174.5° C.                                         Form: Free                                                                    Example 216                                                                   Structure                                                                      -                                                                          9  STR516##                                                                      -                                                                          2  STR517##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 182-183° C.                                             Form: Free                                                                    Example 217                                                                   Structure                                                                      -                                                                          9  STR518##                                                                      -                                                                          3  STR519##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 225.5-226.5° C.                                         Form: Free                                                                    Example 219                                                                   Structure                                                                      -                                                                          8  STR520##                                                                      -                                                                          6  STR521##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 21)                                                             Form: Hydrochloride                                                           Example 220                                                                   Structure                                                                      -                                                                          8  STR522##                                                                      -                                                                          9  STR523##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 147.5-148.5° C.                                         Form: Free                                                                    Example 221                                                                   Structure                                                                      -                                                                          8  STR524##                                                                      -                                                                          1  STR525##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 136-137° C.                                             Form: Free                                                                    Example 222                                                                   Structure                                                                      -                                                                          8  STR526##                                                                      -                                                                          2  STR527##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 191.5-192.5° C.                                         Form: Free                                                                    Example 223                                                                   Structure                                                                      -                                                                          8  STR528##                                                                      -                                                                          4  STR529##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 145-146° C.                                             Form: Free                                                                    Example 224                                                                   Structure                                                                      -                                                                          5  STR530##                                                                      -                                                                          6  STR531##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 22)                                                             Form: Hydrochloride                                                           Example 225                                                                   Structure                                                                      -                                                                          5  STR532##                                                                      -                                                                          7  STR533##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 23)                                                             Form: Hydrochloride                                                           Example 226                                                                   Structure                                                                      -                                                                          5  STR534##                                                                      -                                                                          8  STR535##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 24)                                                             Form: Hydrochloride                                                           Example 227                                                                   Structure                                                                      -                                                                          5  STR536##                                                                      -                                                                          9  STR537##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 25)                                                             Form: Hydrochloride                                                           Example 228                                                                   Structure                                                                      -                                                                          5  STR538##                                                                      -                                                                          1  STR539##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 26)                                                             Form: Hydrochloride                                                           Example 229                                                                   Structure                                                                      -                                                                          5  STR540##                                                                      -                                                                          4  STR541##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      NMR analysis: 27)                                                             Form: Hydrochloride                                                           Example 230                                                                   Structure                                                                      -                                                                          7  STR542##                                                                      -                                                                          0  STR543##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 206-207° C.                                             Form: Free                                                                    Example 231                                                                   Structure                                                                      -                                                                          6  STR544##                                                                      -                                                                          3  STR545##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Chloroform/metahnol                                Melting Point: 211-213° C.                                             Form: Free                                                                    Example 232                                                                   Structure                                                                      -                                                                          7  STR546##                                                                      -                                                                          8  STR547##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Chloroform/metahnol                                Melting Point: 228.5-229.5° C.                                         Form: Free                                                                    Example 233                                                                   Structure                                                                      -                                                                          9  STR548##                                                                      -                                                                          0  STR549##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Chloroform/metahnol                                Melting Point: 237-238° C.                                             Form: Free                                                                    Example 234                                                                   Structure                                                                      -                                                                          1  STR550##                                                                      -                                                                          0  STR551##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Chloroform/metahnol                                Melting Point: 226-228° C.                                             Form: Free                                                                    Example 235                                                                   Structure                                                                      -                                                                          2  STR552##                                                                      -                                                                          0  STR553##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Chloroform/metahnol                                Melting Point: 220-222° C.                                             Form: Free                                                                    Example 236                                                                   Structure                                                                      -                                                                          3  STR554##                                                                      -                                                                          0  STR555##                                                                      - Crystalline form: Colorless amporphous                                     NMR analysis: 28)                                                             Form: Free                                                                    Example 237                                                                   Structure                                                                      -                                                                          4  STR556##                                                                      -                                                                          0  STR557##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 162-165° C.                                             Form: Free                                                                    Example 238                                                                   Structure                                                                      -                                                                          5  STR558##                                                                      -                                                                          6  STR559##                                                                      - Crystalline form: Light brown amorphous                                    NMR analysis: 29)                                                             Form: Free                                                                    Example 239                                                                   Structure                                                                      -                                                                          7  STR560##                                                                      -                                                                          6  STR561##                                                                      - Crystalline form: Light brown amorphous                                    NMR analysis: 30)                                                             Form: Free                                                                    Example 240                                                                   Structure                                                                      -                                                                          8  STR562##                                                                      -                                                                          9  STR563##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 215-217° C.                                             Form: Free                                                                    Example 241                                                                   Structure                                                                      -                                                                          0  STR564##                                                                      -                                                                          9  STR565##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 221-223° C.                                             Form: Free                                                                    Example 242                                                                   Structure                                                                      -                                                                          1  STR566##                                                                      -                                                                          9  STR567##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 31)                                                             Form: Free                                                                    Example 243                                                                   Structure                                                                      -                                                                          2  STR568##                                                                      -                                                                          9  STR569##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 207-210° C.                                             Form: Free                                                                    Example 244                                                                   Structure                                                                      -                                                                          3  STR570##                                                                      -                                                                          9  STR571##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 32)                                                             Form: Free                                                                    Example 245                                                                   Structure                                                                      -                                                                          9  STR572##                                                                      -                                                                          9  STR573##                                                                      - Crystalline form: Colorless amorphous                                      NMR analyss: 33)                                                              Form: Free                                                                    Example 246                                                                   Structure                                                                      -                                                                          4  STR574##                                                                      -                                                                          9  STR575##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 34)                                                             Form: Free                                                                    Example 247                                                                   Structure                                                                      -                                                                          5  STR576##                                                                      -                                                                          9  STR577##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 35)                                                             Form: Free                                                                    Example 248                                                                   Structure                                                                      -                                                                          6  STR578##                                                                      -                                                                          9  STR579##                                                                      - Crystalline form: Light yellow powder                                      Recrystallization solvent: Ethanol                                            Melting Point: 186-187° C.                                             Form: Free                                                                    Example 249                                                                   Structure                                                                      -                                                                          7  STR580##                                                                      -                                                                          8  STR581##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 190-191° C.                                             Form: Free                                                                    Example 250                                                                   Structure                                                                      -                                                                          7  STR582##                                                                      -                                                                          9  STR583##                                                                      - Crystalline form: Light yellow scales                                      Recrystallization solvent: Ethanol/water                                      Melting Point: 230-231° C.                                             Form: Free                                                                    Example 251                                                                   Structure                                                                      -                                                                          7  STR584##                                                                      -                                                                          0  STR585##                                                                      - Crystalline form: Light yellow needles                                     Recrystallization solvent: Ethanol                                            Melting Point: 227-228° C.                                             Form: Free                                                                    Example 252                                                                   Structure                                                                      -                                                                          7  STR586##                                                                      -                                                                          1  STR587##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate                                      Melting Point: 192° C.                                                 Form: Free                                                                    Example 253                                                                   Structure                                                                      -                                                                          7  STR588##                                                                      -                                                                          2  STR589##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 186.5-189° C.                                           Form: Free                                                                    Example 254                                                                   Structure                                                                      -                                                                          7  STR590##                                                                      -                                                                          3  STR591##                                                                      - Crystalline form: Light yellow scales                                      Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 165-167° C.                                             Form: Free                                                                    Example 255                                                                   Structure                                                                      -                                                                          7  STR592##                                                                      -                                                                          4  STR593##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 169-170° C.                                             Form: Free                                                                    Example 256                                                                   Structure                                                                      -                                                                          7  STR594##                                                                      -                                                                          5  STR595##                                                                      - Crystalline form: Colorless scales                                         Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 174-177° C.                                             Form: Free                                                                    Example 257                                                                   Structure                                                                      -                                                                          7  STR596##                                                                      -                                                                          6  STR597##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 114-118° C.                                             Form: Free                                                                    Example 258                                                                   Structure                                                                      -                                                                          7  STR598##                                                                      -                                                                          7  STR599##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 170-172° C.                                             Form: Free                                                                    Example 259                                                                   Structure                                                                      -                                                                          7  STR600##                                                                      -                                                                          8  STR601##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 179-181° C.                                             Form: Free                                                                    Example 260                                                                   Structure                                                                      -                                                                          7  STR602##                                                                      -                                                                          9  STR603##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 118-121° C.                                             Form: Free                                                                    Example 261                                                                   Structure                                                                      -                                                                          7  STR604##                                                                      -                                                                          0  STR605##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 144-148° C.                                             Form: Free                                                                    Example 262                                                                   Structure                                                                      -                                                                          7  STR606##                                                                      -                                                                          1  STR607##                                                                      - Crystalline form: Colorless scales                                         Recrystallization solvent: Ethyl acetate                                      Melting Point: 156-157° C.                                             Form: Free                                                                    Example 263                                                                   Structure                                                                      -                                                                          7  STR608##                                                                      -                                                                          2  STR609##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 204-206° C.                                             Form: Free                                                                    Example 264                                                                   Structure                                                                      -                                                                          7  STR610##                                                                      -                                                                          3  STR611##                                                                      - Crystalline form: Light yellow powder                                      Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 165-167° C.                                             Form: Free                                                                    Example 265                                                                   Structure                                                                      -                                                                          7  STR612##                                                                      -                                                                          4  STR613##                                                                      - Crystalline form: Light yellow amorphous                                   NMR analysis: 36)                                                             Form: Free                                                                    Example 266                                                                   Structure                                                                      -                                                                          7  STR614##                                                                      -                                                                          5  STR615##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 122-124° C.                                             Form: Free                                                                    Example 267                                                                   Structure                                                                      -                                                                          7  STR616##                                                                      -                                                                          6  STR617##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 116-117° C.                                             Form: Free                                                                    Example 268                                                                   Structure                                                                      -                                                                          7  STR618##                                                                      -                                                                          7  STR619##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 121-123° C.                                             Form: Free                                                                    Example 269                                                                   Structure                                                                      -                                                                          7  STR620##                                                                      -                                                                          8  STR621##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate                                      Melting Point: 186-187° C.                                             Form: Free                                                                    Example 270                                                                   Structure                                                                      -                                                                          7  STR622##                                                                      -                                                                          9  STR623##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 139-142° C.                                             Form: Free                                                                    Example 271                                                                   Structure                                                                      -                                                                          7  STR624##                                                                      -                                                                          0  STR625##                                                                      - Crystalline form: Light yellow amorphous                                   NMR analysis: 37)                                                             Form: Free                                                                    Example 272                                                                   Structure                                                                      -                                                                          7  STR626##                                                                      -                                                                          1  STR627##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 149.5-152.5° C.                                         Form: Free                                                                    Example 273                                                                   Structure                                                                      -                                                                          7  STR628##                                                                      -                                                                          2  STR629##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 150-152.5° C.                                           Form: Free                                                                    Example 274                                                                   Structure                                                                      -                                                                          7  STR630##                                                                      -                                                                          3  STR631##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 150° C.                                                 Form: Free                                                                    Example 275                                                                   Structure                                                                      -                                                                          7  STR632##                                                                      -                                                                          4  STR633##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 101-104° C.                                             Form: Free                                                                    Example 276                                                                   Structure                                                                      -                                                                          7  STR634##                                                                      -                                                                          5  STR635##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 120-122° C.                                             Form: Free                                                                    Example 277                                                                   Structure                                                                      -                                                                          7  STR636##                                                                      -                                                                          6  STR637##                                                                      - Crystalline form: Light yellow amorphous                                   NMR analysis: 38)                                                             Form: Free                                                                    Example 278                                                                   Structure                                                                      -                                                                          7  STR638##                                                                      -                                                                          7  STR639##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 183-186° C.                                             Form: Free                                                                    Example 279                                                                   Structure                                                                      -                                                                          7  STR640##                                                                      -                                                                          8  STR641##                                                                      - Crystalline form: Light brown powder                                       Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 139-142° C.                                             Form: Free                                                                    Example 280                                                                   Structure                                                                      -                                                                          7  STR642##                                                                      -                                                                          9  STR643##                                                                      - Crystalline form: Light yellow powder                                      Recrystallization solvent: Ethanol                                            Melting Point: 162-165° C.                                             Form: Free                                                                    Example 281                                                                   Structure                                                                      -                                                                          7  STR644##                                                                      -                                                                          0  STR645##                                                                      - Crystalline form: Light yellow scales                                      Recrystallization solvent: Ethyl acetate                                      Melting Point: 224-227° C.                                             Form: Free                                                                    Example 282                                                                   Structure                                                                      -                                                                          7  STR646##                                                                      -                                                                          1  STR647##                                                                      - Crystalline form: Light yellow amorphous                                   NMR analysis: 39)                                                             Form: Free                                                                    Example 283                                                                   Structure                                                                      -                                                                          7  STR648##                                                                      -                                                                          2  STR649##                                                                      - Crystalline form: Light yellow powder                                      Recrystallization solvent: Ethanol/water                                      Melting Point: 162-164° C.                                             Form: Free                                                                    Example 284                                                                   Structure                                                                      -                                                                          7  STR650##                                                                      -                                                                          3  STR651##                                                                      - Crystalline form: Light yellow powder                                      Recrystallization solvent: Ethanol                                            Melting Point: 238-241° C. (decomposed)                                Form: Free                                                                    Example 285                                                                   Structure                                                                      -                                                                          7  STR652##                                                                      -                                                                          4  STR653##                                                                      - Crystalline form: Light yellow amorphous                                   NMR analysis: 40)                                                             Form: Free                                                                    Example 286                                                                   Structure                                                                      -                                                                          7  STR654##                                                                      -                                                                          5  STR655##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 41)                                                             Form: Free                                                                    Example 287                                                                   Structure                                                                      -                                                                          7  STR656##                                                                      -                                                                          6  STR657##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 168-169° C.                                             Form: Free                                                                    Example 288                                                                   Structure                                                                      -                                                                          7  STR658##                                                                      -                                                                          7  STR659##                                                                      - Crystalline form: Light brown powder                                       Recrystallization solvent: Ethanol                                            Melting Point: 189-191° C.                                             Form: Free                                                                    Example 289                                                                   Structure                                                                      -                                                                          7  STR660##                                                                      -                                                                          8  STR661##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 200-202° C.                                             Form: Free                                                                    Example 290                                                                   Structure                                                                      -                                                                          7  STR662##                                                                      -                                                                          9  STR663##                                                                      - Crystalline form: Colorless scales                                         Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 143-146° C.                                             Form: Free                                                                    Example 291                                                                   Structure                                                                      -                                                                          7  STR664##                                                                      -                                                                          0  STR665##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 117-117.5° C.                                           Form: Free                                                                    Example 292                                                                   Structure                                                                      -                                                                          7  STR666##                                                                      -                                                                          1  STR667##                                                                      - Crystalline form: Light brown powder                                       Recrystallization solvent: Diethyl ether/ethyl acetate                        Melting Point: 225-226° C.                                             Form: Free                                                                    Example 293                                                                   Structure                                                                      -                                                                          7  STR668##                                                                      -                                                                          2  STR669##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethanol                                   Melting Point: 175-176.5° C.                                           Form: Free                                                                    Example 294                                                                   Structure                                                                      -                                                                          7  STR670##                                                                      -                                                                          3  STR671##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 234-236° C.                                             Form: Free                                                                    Example 295                                                                   Structure                                                                      -                                                                          7  STR672##                                                                      -                                                                          4  STR673##                                                                      - Crystalline form: Colorless scales                                         Recrystallization solvent: Ethyl acetate                                      Melting Point: 172-174° C.                                             Form: Free                                                                    Example 296                                                                   Structure                                                                      -                                                                          7  STR674##                                                                      -                                                                          5  STR675##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 154-155° C.                                             Form: Free                                                                    Example 297                                                                   Structure                                                                      -                                                                          7  STR676##                                                                      -                                                                          6  STR677##                                                                      - Crystalline form: Light yellow needles                                     Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 181.5-183.5° C.                                         Form: Free                                                                    Example 298                                                                   Structure                                                                      -                                                                          7  STR678##                                                                      -                                                                          7  STR679##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 173-175° C.                                             Form: Free                                                                    Example 299                                                                   Structure                                                                      -                                                                          7  STR680##                                                                      -                                                                          8  STR681##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 137-138° C.                                             Form: Free                                                                    Example 300                                                                   Structure                                                                      -                                                                          7  STR682##                                                                      -                                                                          9  STR683##                                                                      - Crystalline form: Light yellow amorphous                                   NMR analysis: 42)                                                             Form: Free                                                                    Example 301                                                                   Structure                                                                      -                                                                          7  STR684##                                                                      -                                                                          0  STR685##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Diethyl ether/ethyl acetate                        Melting Point: 129-130° C.                                             Form: Free                                                                    Example 302                                                                   Structure                                                                      -                                                                          7  STR686##                                                                      -                                                                          1  STR687##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 181-183° C.                                             Form: Free                                                                    Example 303                                                                   Structure                                                                      -                                                                          7  STR688##                                                                      -                                                                          2  STR689##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 248-249° C.                                             Form: Free                                                                    Example 304                                                                   Structure                                                                      -                                                                          7  STR690##                                                                      -                                                                          3  STR691##                                                                      - Crystalline form: Light yellow amorphous                                   NMR analysis: 43)                                                             Form: Free                                                                    Example 305                                                                   Structure                                                                      -                                                                          7  STR692##                                                                      -                                                                          4  STR693##                                                                      - Crystalline form: Light yellow needles                                     Recrystallization solvent: Ethanol                                            Melting Point: 94-96° C.                                               Form: Free                                                                    Example 306                                                                   Structure                                                                      -                                                                          7  STR694##                                                                      -                                                                          5  STR695##                                                                      - Crystalline form: Light brown powder                                       Recrystallization solvent: Ethyl acetate                                      Melting Point: 159-161° C.                                             Form: Free                                                                    Example 307                                                                   Structure                                                                      -                                                                          7  STR696##                                                                      -                                                                          6  STR697##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 180-183° C.                                             Form: Free                                                                    Example 308                                                                   Structure                                                                      -                                                                          7  STR698##                                                                      -                                                                          7  STR699##                                                                      - Crystalline form: Light brown powder                                       Recrystallization solvent: Ethanol                                            Melting Point: 177-180° C.                                             Form: Free                                                                    Example 309                                                                   Structure                                                                      -                                                                          7  STR700##                                                                      -                                                                          8  STR701##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 91-93° C.                                               Form: Free                                                                    Example 310                                                                   Structure                                                                      -                                                                          7  STR702##                                                                      -                                                                          9  STR703##                                                                      - Crystalline form: Light brown scales                                       Recrystallization solvent: Ethanol                                            Melting Point: 155-156.5° C.                                           Form: Free                                                                    Example 311                                                                   Structure                                                                      -                                                                          7  STR704##                                                                      -                                                                          0  STR705##                                                                      - Crystalline form: Colorless scales                                         Recrystallization solvent: Ethyl acetate                                      Melting Point: 172.5-175° C.                                           Form: Free                                                                    Example 312                                                                   Structure                                                                      -                                                                          7  STR706##                                                                      -                                                                          1  STR707##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 148-150.5° C.                                           Form: Free                                                                    Example 313                                                                   Structure                                                                      -                                                                          7  STR708##                                                                      -                                                                          2  STR709##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 172-173° C.                                             Form: Free                                                                    Example 314                                                                   Structure                                                                      -                                                                          7  STR710##                                                                      -                                                                          3  STR711##                                                                      - Crystalline form: Colorless scales                                         Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 133-135° C.                                             Form: Free                                                                    Example 315                                                                   Structure                                                                      -                                                                          7  STR712##                                                                      -                                                                          4  STR713##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 217-219° C.                                             Form: Free                                                                    Example 316                                                                   Structure                                                                      -                                                                          7  STR714##                                                                      -                                                                          5  STR715##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate                                      Melting Point: 226-227.5° C.                                           Form: Free                                                                    Example 317                                                                   Structure                                                                      -                                                                          7  STR716##                                                                      -                                                                          6  STR717##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 44)                                                             Form: Free                                                                    Example 318                                                                   Structure                                                                      -                                                                          7  STR718##                                                                      -                                                                          7  STR719##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane                                    Melting Point: 234-235° C.                                             Form: Free                                                                    Example 319                                                                   Structure                                                                      -                                                                          7  STR720##                                                                      -                                                                          8  STR721##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Methanol                                           Melting Point: 218-218.5° C.                                           Form: Free                                                                    Example 320                                                                   Structure                                                                      -                                                                          7  STR722##                                                                      -                                                                          9  STR723##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 202.5-206° C.                                           Form: Free                                                                    Example 321                                                                   Structure                                                                      -                                                                          7  STR724##                                                                      -                                                                          0  STR725##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 174-176° C.                                             Form: Free                                                                    Example 322                                                                   Structure                                                                      -                                                                          7  STR726##                                                                      -                                                                          1  STR727##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 216-218° C.                                             Form: Free                                                                    Example 323                                                                   Structure                                                                      -                                                                          7  STR728##                                                                      -                                                                          2  STR729##                                                                      - Crystalline form: White powder                                             Melting Point: >300° C.                                                NMR analysis: 45)                                                             Form: Free                                                                    Example 324                                                                   Structure                                                                      -                                                                          7  STR730##                                                                      -                                                                          3  STR731##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 250.5-251° C.                                           Form: Free                                                                    Example 325                                                                   Structure                                                                      -                                                                          7  STR732##                                                                      -                                                                          4  STR733##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 223-225° C.                                             Form: Free                                                                    Example 326                                                                   Structure                                                                      -                                                                          7  STR734##                                                                      -                                                                          5  STR735##                                                                      - Crystalline form: Colorless prismsr                                        Recrystallization solvent: Methanol                                           Melting Point: 213-214° C.                                             Form: Free                                                                    Example 327                                                                   Structure                                                                      -                                                                          7  STR736##                                                                      -                                                                          6  STR737##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 246-247° C.                                             Form: Free                                                                    Example 328                                                                   Structure                                                                      -                                                                          7  STR738##                                                                      -                                                                          7  STR739##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Methanol                                           Melting Point: 248-251° C.                                             Form: Free                                                                    Example 329                                                                   Structure                                                                      -                                                                          7  STR740##                                                                      -                                                                          8  STR741##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 268.5-270.5° C.                                         Form: Free                                                                    Example 330                                                                   Structure                                                                      -                                                                          7  STR742##                                                                      -                                                                          9  STR743##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methano/diethyl ether                              Melting Point: 174-176° C.                                             Form: Free                                                                    Example 331                                                                   Structure                                                                      -                                                                          7  STR744##                                                                      -                                                                          0  STR745##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 130-134° C.                                             Form: Free                                                                    Example 332                                                                   Structure                                                                      -                                                                          7  STR746##                                                                      -                                                                          1  STR747##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 214-217° C.                                             Form: Hydrochloride                                                           Example 333                                                                   Structure                                                                      -                                                                          7  STR748##                                                                      -                                                                          2  STR749##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 218-220° C.                                             Form: Hydrochloride                                                           Example 334                                                                   Structure                                                                      -                                                                          7  STR750##                                                                      -                                                                          3  STR751##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 222-225° C.                                             Form: Free                                                                    Example 335                                                                   Structure                                                                      -                                                                          7  STR752##                                                                      -                                                                          4  STR753##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Methanol/ditehyl ether                             Melting Point: 171-172° C.                                             Form: Free                                                                    Example 336                                                                   Structure                                                                      -                                                                          7  STR754##                                                                      -                                                                          5  STR755##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 235.5-236° C.                                           Form: Dihydrochloride                                                         Example 337                                                                   Structure                                                                      -                                                                          7  STR756##                                                                      -                                                                          6  STR757##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 241-243° C.                                             Form: Free                                                                    Example 338                                                                   Structure                                                                      -                                                                          7  STR758##                                                                      -                                                                          7  STR759##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 187-191° C.                                             Form: Free                                                                    Example 339                                                                   Structure                                                                      -                                                                          7  STR760##                                                                      -                                                                          8  STR761##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 240-244° C.                                             Form: Hydrochloride                                                           Example 340                                                                   Structure                                                                      -                                                                          7  STR762##                                                                      -                                                                          9  STR763##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 181-182° C.                                             Form: Free                                                                    Example 341                                                                   Structure                                                                      -                                                                          7  STR764##                                                                      -                                                                          0  STR765##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 188-190° C.                                             Form: Dihydrochloride                                                         Example 343                                                                   Structure                                                                      -                                                                          7  STR766##                                                                      -                                                                          1  STR767##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Isopropyl alcohol                                  Melting Point: 218-218.5° C.                                           Form: Hydrrochloride                                                          Example 343                                                                   Structure                                                                      -                                                                          7  STR768##                                                                      -                                                                          2  STR769##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 243-245.5° C.                                           Form: Free                                                                    Example 344                                                                   Structure                                                                      -                                                                          7  STR770##                                                                      -                                                                          3  STR771##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 130-133° C.                                             Form: Free                                                                    Example 345                                                                   Structure                                                                      -                                                                          7  STR772##                                                                      -                                                                          4  STR773##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 155-158° C.                                             Form: Free                                                                    Example 346                                                                   Structure                                                                      -                                                                          7  STR774##                                                                      -                                                                          5  STR775##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 208-210° C.                                             Form: Hydrochloride                                                           Example 347                                                                   Structure                                                                      -                                                                          7  STR776##                                                                      -                                                                          6  STR777##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 154-155° C.                                             Form: Hydrochloride                                                           Example 348                                                                   Structure                                                                      -                                                                          7  STR778##                                                                      -                                                                          7  STR779##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 142-143° C.                                             Form: Free                                                                    Example 349                                                                   Structure                                                                      -                                                                          7  STR780##                                                                      -                                                                          8  STR781##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 120-125° C.                                             Form: Hydrochloride                                                           Example 350                                                                   Structure                                                                      -                                                                          7  STR782##                                                                      -                                                                          9  STR783##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 91-95° C.                                               Form: Hydrochloride                                                           Example 351                                                                   Structure                                                                      -                                                                          7  STR784##                                                                      -                                                                          0  STR785##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 145-146.5° C.                                           Form: Free                                                                    Example 352                                                                   Structure                                                                      -                                                                          7  STR786##                                                                      -                                                                          1  STR787##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 105-105.5° C.                                           Form: Free                                                                    Example 353                                                                   Structure                                                                      -                                                                          7  STR788##                                                                      -                                                                          2  STR789##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 151-155° C.                                             Form: Dihydrochloride                                                         Example 354                                                                   Structure                                                                      -                                                                          7  STR790##                                                                      -                                                                          3  STR791##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 135.5-137.5° C.                                         Form: Free                                                                    Example 355                                                                   Structure                                                                      -                                                                          7  STR792##                                                                      -                                                                          4  STR793##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 178-178.5° C.                                           Form: Free                                                                    Example 356                                                                   Structure                                                                      -                                                                          7  STR794##                                                                      -                                                                          5  STR795##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane                                    Melting Point: 266.5-268° C.                                           Form: Free                                                                    Example 357                                                                   Structure                                                                      -                                                                          7  STR796##                                                                      -                                                                          6  STR797##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 123-124° C.                                             Form: Free                                                                    Example 358                                                                   Structure                                                                      -                                                                          7  STR798##                                                                      -                                                                          7  STR799##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 212-213.5° C.                                           Form: Free                                                                    Example 359                                                                   Structure                                                                      -                                                                          7  STR800##                                                                      -                                                                          8  STR801##                                                                      - Crystalline form: Colorless scales                                         Recrystallization solvent: Ethyl acetate                                      Melting Point: 160.5-162° C.                                           Form: Free                                                                    Example 360                                                                   Structure                                                                      -                                                                          7  STR802##                                                                      -                                                                          9  STR803##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 103-105° C.                                             Form: Free                                                                    Example 361                                                                   Structure                                                                      -                                                                          7  STR804##                                                                      -                                                                          0  STR805##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 145-146° C.                                             Form: Free                                                                    Example 362                                                                   Structure                                                                      -                                                                          7  STR806##                                                                      -                                                                          1  STR807##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 247-250° C.                                             Form: Free                                                                    Example 363                                                                   Structure                                                                      -                                                                          7  STR808##                                                                      -                                                                          2  STR809##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 198-199° C.                                             Form: Free                                                                    Example 364                                                                   Structure                                                                      -                                                                          7  STR810##                                                                      -                                                                          3  STR811##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 181.5-182.5° C.                                         Form: Free                                                                    Example 365                                                                   Structure                                                                      -                                                                          7  STR812##                                                                      -                                                                          4  STR813##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 170-170.5° C.                                           Form: Free                                                                    Example 366                                                                   Structure                                                                      -                                                                          7  STR814##                                                                      -                                                                          5  STR815##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 156-158° C.                                             Form: Hydrochloride                                                           Example 367                                                                   Structure                                                                      -                                                                          7  STR816##                                                                      -                                                                          6  STR817##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether                                      Melting Point: 168.5-170.5° C.                                         Form: Free                                                                    Example 368                                                                   Structure                                                                      -                                                                          7  STR818##                                                                      -                                                                          7  STR819##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 177-181.5° C.                                           Form: Hydrochloride                                                           Example 369                                                                   Structure                                                                      -                                                                          7  STR820##                                                                      -                                                                          8  STR821##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 211-213° C.                                             Form: Free                                                                    Example 370                                                                   Structure                                                                      -                                                                          7  STR822##                                                                      -                                                                          9  STR823##                                                                      - Crystalline form: White powder                                             NMR analysis: 46)                                                             Form: Free                                                                    Example 371                                                                   Structure                                                                      -                                                                          7  STR824##                                                                      -                                                                          0  STR825##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 166-167° C.                                             Form: Free                                                                    Example 372                                                                   Structure                                                                      -                                                                          7  STR826##                                                                      -                                                                          1  STR827##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 127-131° C.                                             Form: Free                                                                    Example 373                                                                   Structure                                                                      -                                                                          7  STR828##                                                                      -                                                                          2  STR829##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 170-171° C.                                             Form: Free                                                                    Example 374                                                                   Structure                                                                      -                                                                          7  STR830##                                                                      -                                                                          3  STR831##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 125-126° C.                                             Form: Free                                                                    Example 375                                                                   Structure                                                                      -                                                                          4  STR832##                                                                      -                                                                          5  STR833##                                                                      - Crystalline form: Light yellow amorphous                                   NMR analysis: 47)                                                             Form: Hydrochloride                                                           Example 376                                                                   Structure                                                                      -                                                                          4  STR834##                                                                      -                                                                          6  STR835##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 48)                                                             Form: Free                                                                  ______________________________________                                          1)     .sup.1 H--NMR(CDCl.sub.3)δ: 1.92(1H, t, J=6.2Hz), 1.98                    (1H, t, J=6.4Hz), 2.8(2H, t, J=6.4Hz), 3.76                           (2H, t, J=6.2Hz), 6.75(1H, d, J=7.6Hz), 6.86                                  (2H, d, J=8.6Hz), 6.8-7.1(2H, m), 7.20(1H, d,                                 J=7Hz), 7.30(2H, d), J=8.6Hz), 7.71(2H, d,                                    J=8.6Hz), 7.84(2H, d, J=8.6Hz), 10.13(1H, s)                                 2) .sup.1 H--NMR(DMSO-d.sub.6)δ: 2.05(2H, quint, J=6.4Hz),                       2.91(2H, t, J=6.4Hz), 3.86(2H, t, J=6.4Hz),                           6.85(1H, d, J=7.6Hz), 6.9-7.2(2H, m), 7.30(1H,                                d, J=7.2Hz), 7.44(2H, d, J=8.5Hz), 7.85(2H, d,                                J=8.5Hz), 8.1-8.2(4H, m), 10.65(1H, s), 13.2-                                 13.4(1H, br)                                                                 3) .sup.1 H--NMR(CDCl.sub.3)δ: 1.9-2.1(2H, m), 2.84(2H, t,                       J=6.5Hz), 3.82(6H, s), 3.90(2H, t, J=6.6Hz),                          6.5-7.2(7H, m), 7.35(2H, d, J=8.7Hz), 7.55(2H,                                d, J=8.7Hz), 8.05(1H, s)                                                     4) .sup.1 H--NMR(CDCl.sub.3)δ: 1.9-2.1(2H, m), 2.37(6H,                  s), 2.84(2H, t), J=6.6Hz), 3.90(2H, t, J=6.6Hz),                              6.71(1H, d, J=7.9Hz), 6.8-7.2(4H, m), 7.35(2H,                                d, J=8.6Hz), 7.44(2H, s), 7.56(2H, d), J=8.6Hz),                              8.00(1H, s)                                                                  5) .sup.1 H--NMR(CDCl.sub.3)δ: 1.9-2.2(2H, m), 2.12(3H,                  s), 2.84(2H, t, J=6.6Hz), 3.89(2H, t, J=6.5Hz),                               6.71(1H, d, J=7.8Hz), 6.87(1H, t, J=7Hz), 6.99                                (1H, t, J=7.3Hz), 7.15(1H, d, J=6.5Hz), 7.28                                  (2H, d, J=8.6Hz), 7.41(2H, d, J=8,6Hz), 8.03                                  (1H, s)                                                                      6) .sup.1 H--NMR(CDCl.sub.3)δ: 0.8-1.3(6H, m), 1.6-2.3(9H,                       m), 2.83(2H, t, J=6.6Hz), 3.89(2H, t, J=6.5Hz),                       6.72(1H, d, J=7.9Hz), 6.8-7.1(2H, m), 7.15(1H,                                d, J=7.4Hz), 7.28(2H, d, J=8.3Hz), 7.44(2H, d,                                J=8.4Hz), 7.9-8.1(1H, m)                                                     7) .sup.1 H--NMR(CDCl.sub.3)δ: 2.02(2H, quint, J=6.5Hz),                 2.81(2H, t, J=6.6Hz), 3.69(2H, s), 3.87(2H, t,                                J=6.6Hz), 6.66(1H, d, J=8.2Hz), 6.8-7.0(2H, m),                               7.13(1H, d, J=7.3Hz), 7.2-7.4(9H, m), 7.59(1H,                                s)                                                                           8) .sup.1 H--NMR(CDCl.sub.3)δ: 1.7-2.1(17H, m), 2.83(2H, t,                      J=6.7Hz), 3.90(2H, t, J=6.6Hz), 6.68(1H, d,                           J=8.1Hz), 6.8-7.1(2H, m), 7.14(1H, d, J=7Hz),                                 7.32(2H, d, J=8.7Hz), 7.39(1H, s), 7.46(2H, d,                                J=8.7Hz)                                                                     9) .sup.1 H--NMR(CDCl.sub.3)δ: 1.99(2H, quint, J=6.5Hz),                 2.82(2H, t, J=6.6Hz), 3.82(2H, t, J=6.5Hz),                                   6.8-7.1(4H, m), 7.1-7.3(2H, m), 7.4-7.6(3H, m),                               7.67(1H, s), 7.8-8.0(3H, m), 8.43(1H, s)                                     10) .sup.1 H--NMR(CDCl.sub.3)δ: 2.00(2H, quint, J=6.5Hz),                        2.83(2H, t, J=6.6Hz), 3.85(2H, t, J=6.6Hz),                           3.86(3H, s), 6.8-7.1(6H, m), 7.1-7.3(2H, m),                                  7.64(1H, s), 7.8-8.0(3H, m), 8.22(1H, s)                                     11) .sup.1 H--NMR(CDCl.sub.3)δ: 1.98(2H, quint, J=6.5Hz),                        2.82(2H, t, J=6.5Hz), 3.81(2H, t, J=6.5Hz),                           3.84(3H, s), 6.8-7.5(10H, m), 7.68(1H, s), 7.95                               (1H, d, J=8.2Hz), 8.52(1H, s)                                                12) .sup.1 H--NMR(CDCl.sub.3)δ: 1.7-1.9(2H, m), 2.70(2H, t,                      J=6.6Hz), 3.70(2H, t, J=6.4Hz), 6.8-7.3(6H, m),                       7.4-7.7(2H, m), 7.8-7.9(5H, m), 8.04(1H, d, J=8                               Hz), 8.33(1H, s), 8.90(1H, s)                                                13) .sup.1 H--NMR(CDCl.sub.3)δ: 1.7-2.1(17H, m), 2.84(2H, t,                     J=6.5Hz), 3.89(2H, t, J=6.4Hz), 6.8-7.2(6H, m),                       7.42(1H, s), 7.56(1H, s), 7.81(1H, d, J=8.1Hz)                               14) .sup.1 H--NMR(DMSO-d.sub.6)δ: 1.0-1.5(5H, m), 1.5-2.0(5H,                    m), 2.2-3.8(8H, m), 4.2-5.2(3H, m), 6.77(1H, d,                       J=7.2Hz), 7.1-7.4(4H, m), 7.47(2H, d, J=8.6Hz),                               7.58(1H, d, J=6.2Hz), 10.06(1H, s), 10.9-12.1                                 (1H, br)                                                                     15) .sup.1 H--NMR(DMSO-d.sub.6)δ: 2.5-3.8(6H, m), 4.2-5.2(3H,                    m), 6.81(1H, d, J=6.8Hz), 7.1-7.3(4H, m), 7.5-                        7.7(3H, m), 7.8-8.0(1H, m), 7.97(2H, d, J=1.8                                 Hz), 10.66(1H, s), 11.1-12.3(1H, br)                                         16) .sup.1 H--NMR(DMSO-d.sub.6)δ: 2.20(3H, s), 2.27(3H, s),                      2.5-3.8(6H, m), 4.3-5.3(3H, m), 6.82(1H, d,                           J=7.2Hz), 7.1-7.4(7H, m), 7.5-7.8(3H, m), 10.43                               (1H, s), 11.0-12.2(1H, br)                                                   17) .sup.1 H--NMR(DMSO-d.sub.6)δ: 2.34(3H, s), 2.5-3.7(6H, m),                   4.3-5.2(3H, m), 6.82(1H, d, J=6.8Hz), 7.2-7.7                         (11H, m), 10.41(1H, s), 10.8-12.3(1H, br)                                    18) .sup.1 H--NMR(DMSO-d.sub.6)δ: 2.38(3H, s), 2.5-3.8(6H, m),                   4.3-5.3(3H, m), 6.81(1H, d, J=7.0Hz), 7.1-7.5                         (6H, m), 7.5-7.8(5H, m), 10.35(1H, s), 10.9-12.2                              (1H, br)                                                                     19) .sup.1 H--NMR(DMSO-d.sub.6)δ: 2.37(3H, s), 2.5-3.7(6H, m),                   4.3-5.2(3H, m), 6.81(1H, d, J=7.2Hz), 7.2-7.4                         (6H, m), 7.5-7.7(3H, m), 7.84(2H, d, J=8.0Hz),                                10.31(1H, s), 10.9-12.2(1H, br)                                              20) .sup.1 H--NMR(DMSO-d.sub.6)δ: 2.5-3.8(6H, m), 4.3-5.2(3H,                    m), 6.82(1H, d, J=7.4Hz), 7.2-7.3(4H, m), 7.5-                        7.8(5H, m), 7.75(1H, d, J=1.8Hz), 10.70(1H, s),                               10.8-12.2(1H, br)                                                            21) .sup.1 H--NMR(DMSO-d.sub.6)δ: 2.5-3.8(9H, m), 4.3-4.7(1H,                    m), 4.7-5.1(2H, m), 6.8-7.1(3H, m), 7.1-7.4(2H,                       m, 7.5-7.7(2H, m), 7.8-8.0(3H, m), 9.79(1H, s),                               10.8-12.2(1H, br)                                                            22) .sup.1 H--NMR(DMSO-d.sub.6)δ: 0.8-1.2(3H, m), 1.7-2.2(2H,                    m), 2.5-3.8(5H, m), 4.3-5.2(32H, m), 6.80(1H, d,                      J=7.2Hz), 7.1-7.3(4H, m), 7.6-7.7(3H, m), 7.85                                (1H, s), 7.96(2H, d, J=1.8Hz), 10.62(1H, s),                                  10.8-12.0(1H, br)                                                            23) .sup.1 H--NMR(DMSO-d.sub.6)δ: 0.8-1.1(3H, m), 1.7-2.1(2H,                    m), 2.37(3H, s), 2.7-3.8(5H, m), 4.4-5.2(3H, m),                      6.81(1H, d, J=7.6Hz), 7.2-7.4(6H, m), 7.6-7.7                                 (3H, m), 7.84(2H, d, J=8.2Hz), 10.29(1H, s),                                  10.5-11.8(1H, br)                                                            24) .sup.1 H--NMR(DMSO-d.sub.6)δ: 0.8-1.2(3H, m), 1.71-2.1(2H,                   m), 2.38(3H, s), 2.6-3.8(5H, m), 4.3-5.2(3H, m),                      6.81(1H, d, J=7.0Hz), 7.2-7.5(6H, m), 7.6-7.8                                 (5H, m), 10.33(1H, s), 10.5-11.7(1H, br)                                     25) .sup.1 H--NMR(DMSO-d.sub.6)δ: 0.8-1.2(3H, m), 1.7-2.1(2H,                    m), 2.6-3.8(5H, m), 3.8-5.2(3H, m), 6.82(1H, d,                       J=7.2Hz), 7.1-7.5(8H, m), 7.5-7.76(3H, m), 10.42                              (1H, s), 10.7-12.0(1H, br)                                                   26) .sup.1 H--NMR(DMSO-d.sub.6)δ: 0.8-2.0(15H, m), 2.2-2.5(1H,                   m), 2.6-3.7(5H, m), 4.3-5.2(3H, m), 6.76(1H, d,                       J=7.0Hz), 7.1-7.4(4H, m), 7.46(2H, d, J=8.6Hz),                               7.61(1H, d, J=6.4Hz), 10.03(1H, s), 10.5-11.8                                 (1H, br)                                                                     27) .sup.1 H--NMR(DMSO-d.sub.6)δ: 0.8-1.1(3H, m), 1.7-2.0(2H,                    m), 2.20(3H, s), 2.29(3H, s), 2.6-3.7(5H, m),                         4.3-5.2(3H, m), 6.82(1H, d, J=7.0Hz), 7.2-7.4                                 (7H, m), 7.5-7.7(3H, m), 10.41(1H, s), 10.6-12.0                              (1H, br)                                                                     28) .sup.1 H--NMR(CDCl.sub.3)δ: 1.21(3H, t, J=7.1Hz), 3.00-                      3.25(3H, m), 4.00-4.30(4H, m), 6.63(1H, d, J=7.8                      Hz), 6.86(1H, t, J=7.3Hz), 7.00(1H, t, J=6.3                                  Hz), 7.10-7.31(3H, m), 7.40-7.57(3H, m), 7.77                                 (2H, d, J=1.9Hz), 8.76(1H, brs)                                              29) .sup.1 H--NMR(CDCl.sub.3)δ: 2.29(3H, s), 2.32(3H, s), 2.34                   (3H, s), 2.50-3.15(11H, m), 3.79(1H, dd, J=13.2                       Hz), 7.3Hz), 4.05(1H, dd, J=13.2Hz, 5.7Hz), 6.62                              (1H, d, J=7.7Hz), 6.82-7.48(8H, m), 7.53(2H, d,                               J=8.4Hz), 8.05(1H, brs)                                                      30) .sup.1 H--NMR(CDCl.sub.3)δ: 1.65-2.01(4H, m), 2.31(3H,                       s), 2.35(3H, s), 2.55-3.02(6H, m), 3.09(1H, dd,                       J=15Hz, 5Hz), 3.70(1H, dd), J=12.5Hz, 8.0Hz),                                 4.22(1H, dd, J=12.5Hz, 5Hz), 6.67(1H, d, J=7.8                                Hz), 6.80-7.32(7H, m), 7.37(2H, d, J=8.6Hz),                                  7.53(1H, d, J=8.3Hz), 7.66(1H, brs)                                          31) .sup.1 H--NMR(CDCl.sub.3)δ: 2.80(1H, dd, J=16.1Hz, 5.3                       Hz), 3.16(1H, dd, J=15.8Hz, 5.3Hz), 3.75-4.50                         (3H, m), 4.87-5.10(3H, m), 6.80-7.60(14H, m),                                 7.74(2H, d, J=1.9Hz), 8.47(1H, brs)                                          32) .sup.1 H--NMR(CDCl.sub.3)δ: 2.35(6H, s), 2.72-3.10(3H,                       m), 3.65-3.78(1H, m), 4.06-4.18(1H, m), 6.60-7.62                     (9H, m), 7.74(2H, d, J=1.8Hz), 8.52(1H, brs)                                 33) .sup.1 H--NMR(CDCl.sub.3)δ: 1.87(3H, s), 2.68(1H, dd,                        J=5.6Hz, 16Hz), 3.14(1H, dd, J=5.6Hz, 16Hz),                          3.70-3.95(2H, m), 4.32-4.50(1H, m), 6.29(1H, d,                               J=7.6Hz), 6.90-7.80(11H, m), 9.16(1H, brs)                                   34) .sup.1 H--NMR(CDCl.sub.3)δ: 1.62(1H, brs), 1.90-2.25(2H,                     m), 2.55(3H, s), 3.78(1H, t, J=5.1Hz), 3.95(2H,                       t, J=6.7Hz), 6.69(1H, t, J=7.9Hz), 6.90-7.13                                  (2H, m), 7.23-7.40(3H, m), 7.42-7.56(3H, m), 7.77                             (2H, d, J=1.9Hz), 8.53(1H, brs)                                              35) .sup.1 H--NMR(CDCl.sub.3)δ: 1.80-2.02(1H, m), 2.20-2.35                      (1H, m), 2.31(6H, s), 3.52(1H, t, J=5.4Hz),                           3.68-3.83(1H, m), 3.95-4.15(1H, m), 6.59(1H, d,                               J=7.8Hz), 6.81-7.10(2H, m), 7.16-7.50(6H, m),                                 7.80(2H, d, J=1.8Hz), 9.13(1H, brs)                                          36) .sup.1 H--NMR(CDCl.sub.3)δ: 1.35-1.60(1H, m), 1.65-2.20                      (3H, m), 2.65-3.20(5H, m), 3.81(2H, d, J=6.5Hz),                      4.90-5.10(1H, m), 6.60(1H, d, J=8.0Hz), 6.90                                  (1H, t, J=8.0Hz), 7.00-7.50(6H, m)                                           37) .sup.1 H--NMR(CDCl.sub.3)δ: 1.30-2.25(4H, m), 2.55-3.20                      (3H, m), 3.35(2H, s), 3.80(2H, s), 4.90-5.10(1H,                      m), 6.62(1H, d, J=8.0Hz), 6.85-7.45(12H, m),                                  9.27(1H, br)                                                                 38) .sup.1 H--NMR(CDCl.sub.3)δ: 1.35-2.25(4H, m), 2.33(3H, s),                   2.60-3.20(3H, m), 3.12(2H, s), 3.61(2H, s), 5.00                      (1H, brs), 6.50-7.60(13H, m), 9.14(1H, brs)                                  39) .sup.1 H--NMR(CDCl.sub.3)δ: 1.27(3H, t, J=7.1Hz), 1.25-                      2.50(12H, m), 2.70-3.10(4H, m), 3.05(2H, s),                          4.15(2H, q, J=7.0Hz), 4.90-5.10(1H, m), 6.63                                  (1H, d, J=7.5Hz), 6.91(1H, t, J=7.5Hz), 7.00-                                 7.50(6H, m), 9.14(1H, brs)                                                   40) .sup.1 H--NMR(CDCl.sub.3)δ: 1.30-1.65(1H, m), 1.80-2.25                      (5H, m), 2.70-3.20(3H, m), 4.01(2H, d, J=5.0Hz),                      4.90-5.10(1H, m), 6.61(1H, d, J=7.7Hz), 6.89                                  (1H, t, J=7.0Hz), 7.00-7.45(6H, m), 9.05(1H,                                  brs)                                                                         41) .sup.1 H--NMR(CDCl.sub.3)δ: 1.18(6H, s), 1.30-2.20(4H, m),                   2.60-3.20(3H, m), 3.30(2H, s), 3.373(2H, s),                          4.90-5.10(1H, m), 6.61(1H, d, J=7.3Hz), 6.70-                                 7.45(12H, m), 9.50(1H, brs)                                                  42) .sup.1 H--NMR(CDCl.sub.3)δ: 1.19(3H, t, J=7.0Hz), 1.30-                      1.70(1H, m), 1.75-2.20(3H, m), 2.65-3.15(3H, m),                      3.46(2H, q, J=7.0Hz), 3.88(2H, s), 4.90-5.10                                  (1H, m), 6.55-7.45(13H, m), 8.36(1H, brs)                                    43) .sup.1 H--NMR(CDCl.sub.3)δ: 1.08(3H, t, J=7.2Hz), 1.05-                      2.25(14H, m), 2.25-3.25(10H, m), 4.90-5.10(1H,                        m), 6.64(1H, d, J=7.6Hz), 6.90(1H, t, J=7.2Hz),                               6.94-7.50(6H, m), 11.50(1H, brs)                                             44) .sup.1 H--NMR(CDCl.sub.3)δ: 1.06(3H, t, J=7.5Hz), 1.30-                      2.20(6H, m), 2.60-3.20(3H, m), 3.65(1H, m), 3.95                      (1H, brs), 4.90-5.10(1H, m), 6.50-6.75(3H, m),                                6.75-7.05(2H, m), 7.05-7.55(8H, m), 8.67(1H,                                  brs)                                                                         45) .sup.1 H--NMR(DMSO-d.sub.6)δ: 1.28-1.57(1H, m), 1.69-2.20                    (3H, m), 2.59-3.15(3H, m), 4.74-4.98(1H, m),                          6.62-6.80(1H, m), 6.86-7.37(5H, m), 7.50-7.70                                 (2H, m), 8.95-9.02(1H, m), 9.03-9.15(2H, m),                                  10.85(1H, s)                                                                 46) .sup.1 H--NMR(CDCl.sub.3)δ: 1.40-1.66(5H, m), 1.72-2.20                      (7H, m), 2.63-3.18(3H, m), 3.42(2H, t, J=6.7Hz),                      4.00(2H, t, J=6.3Hz), 4.91-5.13(1H, m), 6.58-                                 6.72(1H, m), 6.82-7.00(3H, m), 7.02-7.30(4H, m),                              7.36-7.51(2H, m), 7.70-7.88(2H, m), 7.91(1H, s)                              47) .sup.1 H--NMR(DMSO-d.sub.6)δ: 2.05-2.95(8H, m), 3.43-3.70                    (1H, m), 4.08-4.30(1H, m), 4.72-5.00(1H, m),                          6.70-8.08(11H, m), 10.8(1H, s), 11.1(1H, brs)                                48) .sup.1 H--NMR(DMSO-d.sub.6)δ: 2.10-3.00(8H, m), 3.47-3.70                    (1H, m), 4.07-4.33(1H, m), 4.75-4.98(1H, m),                          6.78-6.91(1H, m), 7.05-7.22(2H, m), 7.30-7.97                                 (9H, m), 10.75(1H, s), 10.94(1H, brs)                                      ______________________________________                                    

EXAMPLE 377

To a solution of1-[4-(4-formylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.3 g)in methanol (10 ml) is added gradually sodium borohydride (59 mg) underice-cooling and the mixture is stirred at room temperature for 2 hours.Water is added to the mixture and the solvent is distilled off underreduced pressure. The resulting residue is extracted withdichloromethane, washed with water, and dried over magnesium sulfate.The solvent is distilled off under reduced pressure and the resultingresidue is purified by silica gel column chromatography (eluent;dichloromethane:methanol=50:1), and recrystallized from methanol to give1-[4-(4-hydroxymethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(165 mg) as white powder, m.p. 224.5-225.5° C.

Using the suitable starting materials, the compound of the above Example37 is obtained in the same manner as in Example 377.

EXAMPLE 378

To a solution of1-[4-(4-methoxycarbonylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.5 g) in methanol (20 ml) is added 5% aqueous sodium hydroxidesolution (10 ml) and the mixture is stirred at room temperatureovernight. Methanol is distilled off under reduced pressure and theresulting residue is acidified with diluted aqueous hydrochloric acidsolution. The precipitated crystal is collected by filtration to give1-[4-(4-carboxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.4 g)as white powder, m.p. >300° C.

¹ H-NMR (DMSO-d₆) δ: 2.05 (2H, quint, J=6.4 Hz), 2.91 (2H, t, J=6.4 Hz),3.86 (2H, t, J=6.4 Hz), 6.85 (1H, d, J=7.6 Hz), 6.9-7.2 (2H, m), 7.30(1H, d, J=7.2 Hz), 7.44 (2H, d, J=8.5 Hz), 7.85 (2H, d, J=8.5 Hz),8.1-8.2 (4H, m), 10.65 (1H, s), 13.2-13.4 (1H, br)

Using the suitable starting materials, the compounds of the aboveExamples 39, 241, 252, 253 and 362 are obtained in the same manner as inExample 378.

EXAMPLE 379

To a solution of1-[4-(3-acetyloxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (1.5g) in methanol (20 ml) is added 5% aqueous sodium hydroxide solution (10ml) and the mixture is stirred at room temperature overnight. Methanolis distilled off under reduced pressure and the resulting residue isacidified with diluted aqueous hydrochloric acid solution. Theprecipitated crystal is collected by filtration and recrystallized frommethanol to give1-[4-(3-hydroxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (1.22g) as white powder, m.p. 217-218° C.

Using the suitable starting materials, the compounds of the aboveExamples 10, 343, 356, 364 and 365 are obtained in the same manner as inExample 379.

EXAMPLE 380

To a solution of1-[4-(3-hydroxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.4 g)in acetone (5 ml) are added potassium carbonate (0.22 g) and ethyliodide (0.34 g), and the mixture is refluxed for 5 hours. Then, acetoneis distilled off under reduced pressure and water is added to theresidue. The precipitated crystal is collected by filtration, andrecrystallized from methanol to give1-[4-(3-ethoxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.36 g)as white powder, m.p. 170.5-171.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 11, 12, 13, 14, 33, 35, 48, 50-55, 90-92, 97-100, 109-111,120-122, 136-138, 165-167, 175-177, 192-194, 211, 212, 214, 321, 322,330-333, 335, 336, 339-342, 344-355, 357-366 and 370-374 are obtained inthe same manner as in Example 380.

EXAMPLE 381

Ethanol (50 ml) is added to 10% Pd-C (0.1 g) and thereto is added1-[4-(3-nitrobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.73 g).The mixture is subjected to catalytic reduction at ordinary temperatureunder atmospheric pressure of hydrogen. After completion of thereduction, 10% Pd-C is removed by filtration and the filtrate isconcentrated under reduced pressure. The residue is extracted withdichloromethane and the extract is dried over magnesium sulfate. Thesolvent is distilled off under reduced pressure and recrystallized frommethanol to give1-[4-(3-aminobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.54 g)as white powder, m.p. 205.5-206.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 24, 334 and 338 are obtained in the same manner as in Example381.

EXAMPLE 382

To a solution of 1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline (0.5 g)in dichloromethane (20 ml) is added triethylamine (0.3 g), and theretois added benzoyl chloride (0.28 g) under ice-cooling. The mixture isstirred at room temperature for 1 hour. To the reaction mixture is addedwater and extracted with dichloromethane. The extract is dried overmagnesium sulfate and the solvent is distilled off under reducedpressure. The resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=50:1) andrecrystallized from methanol to give1-[4-(benzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (245 mg) aswhite powder, m.p. 202.5-203.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 2-119, 131-373, 375 and 376 are obtained in the same manner asin Example 382.

EXAMPLE 383

Thionyl chloride (10 ml) is added to1-(4-carboxybenzoyl)-1,2,3,4-tetrahydroquinoline (0.5 g) and the mixtureis refluxed for 1 hour. Thionyl chloride is distilled off under reducedpressure to give 4-[1-(1,2,3,4-tetrahydroquinolyl)carbonyl]benzoylchloride. Separately, to a solution of m-anisidine (0.27 g) indichloromethane (20 ml) is added triethylamine (0.34 g), and thereto isadded gradually the above obtained4-[1-(1,2,3,4-tetrahydroquinolyl)carbonyl]benzoyl chloride underice-cooling and the mixture is stirred at room temperature for 1 hour.Water is added to the reaction mixture and the mixture is extracted withdichloromethane. The extract is dried over magnesium sulfate. Thesolvent is distilled off under reduced pressure and the resultingresidue is purified by silica gel column chromatography (eluent;dichloromethane:methanol=50:1), and recrystallized from methanol to give1-[4-(3-methoxyanilinocarbonyl)benzoyl]-1,2,3,4-tetrahydroquinoline (203mg) as colorless needles, m.p. 154-155° C.

Using the suitable starting materials, the compounds of the aboveExamples 120, 122-130 and 374 are obtained in the same manner as inExample 383.

EXAMPLE 384

To4-oxo-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.7g) are added tetrahyrdofuran (10 ml) and methanol (10 ml). To themixture is added sodium borohydride (0.1 g) in portions and the mixtureis stirred at room temperature for 1 hour. Water is added to thereaction mixture and the mixture is extracted with dichloromethane. Thesolvent is concentrated and the resulting residue is purified by silicagel column chromatography (eluent;dichloromethane→dichloromethane:methanol=20:1), and recrystallized fromethanol to give4-hydroxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.4 g) as white powder, m.p. 215-217° C.

EXAMPLE 385

To3-ethoxycarbonyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.6 g) are added an aqueous solution of sodium hydroxide (0.1 g) inwater (1 ml) and ethanol (5 ml). The mixture is stirred at roomtemperature for 15 minutes, and acidified with diluted hydrochloricacid, extracted with dichloromethane. The solvent is distilled off andthe resulting residue is purified by silica gel column chromatography(eluent; dichloromethane→dichloromethane:methanol=50:1), andrecrystallized from ethanol to give3-carboxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.4 g) as white powder, m.p. 221-223° C.

EXAMPLE 386

To3-carboxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(3.7 g) are added tetrahydrofuran (50 ml) and thionyl chloride (5 ml).The mixture is reacted at 60° C. for 1 hour. The reaction mixture isconcentrated and to the residue is added acetone (20 ml). To the mixtureis added dropwise a solution of sodium azide (1.0 g) in water (5 ml)under ice-cooling. The reaction mixture is stirred at the sametemperature for 30 minutes and extracted with dichloromethane, driedover magnesium sulfate. The solvent is concentrated and to the resultingresidue are added anhydrous toluene (30 ml) and benzyl alcohol (1.7 g).The mixture is refluxed for 1 hour. The reaction mixture is concentratedand the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane→dichloromethane:methanol=50:1)to give3-benzyloxycarbonylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl)-1,2,3,4-tetrahydroquinoline(3.7 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ: 2.80 (1H, dd, J=16.1 Hz, 5.3 Hz), 3.16 (1H, dd,J=15.8 Hz, 5.3 Hz), 3.75-4.50 (3H, m), 4.87-5.10 (3H, m), 6.80-7.60(14H, m), 7.74 (2H, d, J=1.9 Hz), 8.47 (1H, brs)

EXAMPLE 387

To3-benzyloxycarbonylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(3.3 g) are added acetic acid (40 ml) and 10% Pd-C (0.4 g) and thereaction mixture is subjected to catalytic reduction at ordinarytemperature under atmospheric pressure of hydrogen. One hour thereafter,the catalyst is removed by filtration and the filtrate is concentrated.The resulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=20:1), and recrystallized from ethanolto give3-amino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(1.6 g) as white powder, m.p. 207-210° C.

EXAMPLE 388

To3-amino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.5 g) are added methanol (10 ml), 37% formaline (0.8 ml) and sodiumcyanoborohydride (0.16 g). To the mixture is added acetic acid (0.5 ml)under ice-cooling and the mixture is stirred at room temperature for 1hour. Water is added to the reaction mixture and the mixture is basifiedwith potassium carbonate and extracted with dichloromethane. The solventis concentrated and the resulting residue is purified by silica gelcolumn chromatography (eluent;dichloromethane→dichloromethane:methanol=20:1) to give3-dimethylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.3 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ: 2.35 (6H, s), 2.72-3.10 (3H, m), 3.65-3.78 (1H, m),4.06-4.18 (1H, m), 6.60-7.62 (9H, m), 7.74 (2H, d, J=1.8 Hz), 8.52 (1H,brs)

Using the suitable starting materials, the compounds of the aboveExamples 246, 247, 375 and 376 are obtained in the same manner as inExample 388.

EXAMPLE 389

To3-amino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.44 g) are added dichloromethane (5 ml) and acetic anhydride (0.12 g)and the mixture is stirred for 1 hour. The reaction mixture isconcentrated and the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane→dichloromethane:methanol=50:1)to give3-acetylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.3 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ: 1.87 (3H, s), 2.68 (1H, dd, J=5.6 Hz, 16 Hz), 3.14(1H, dd, J=5.6 Hz, 16 Hz), 3.70-3.95 (2H, m), 4.32-4.50 (1H, m), 6.29(1H, d, J=7.6 Hz), 6.90-7.80 (11H, m), 9.16 (1H, brs)

Using the suitable starting materials, the compound of the above Example242 is obtained in the same manner as in Example 389.

EXAMPLE 390

To4-oxo-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.5g) are added 40% solution of methylamine in methanol (5 ml), molecularsieves 4A (1 g) and dimethylformamide (6 ml), and the mixture isrefluxed for 4 hours. After cooling, the reaction mixture is filteredand to the filtrate is added sodium borohydride (80 mg), and the mixtureis stirred at room temperature for 1 hour. The reaction mixture isconcentrated and water is added to the resulting residue, and extractedwith ethyl acetate. The solvent is concentrated and the resultingresidue is purified by silica gel column chromatography (eluent;dichloromethane:methanol=20:1) to give4-methylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.2 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ: 1.62 (1H, brs), 1.90-2.25 (2H, m), 2.55 (3H, s), 3.78(1H, t, J=5.1 Hz), 3.95 (2H, t, J=6.7 Hz), 6.99 (1H, d, J=7.9 Hz),6.90-7.13 (2H, m)

Using the suitable starting materials, the compounds of the aboveExamples 238, 239, 244, 247, 375 and 376 are obtained in the same manneras in Example 390.

EXAMPLE 391

To3-carboxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.7 g) are added dimethylformamide (7 ml), diethyl cyanophosphate (0.3ml) and dimethylamine hydrochloride (0.15 g). Further thereto is addedtriethylamine (0.8 ml) and the mixture is stirred at room temperaturefor 1 hour. Water is added to the reaction mixture and extracted withethyl acetate. The solvent is concentrated and to the resulting residueis added diethyl ether. The precipitated crystal is collected byfiltration to give3-dimethylamido-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.5 g) as light yellow powder, m.p. 186-187° C.

EXAMPLE 392

To a solution of 1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(3.0 g) in dichloromethane (50 ml) is added succinic anhydride (1.4 g)and the mixture is stirred at room temperature for 4.5 hours. Thereaction mixture is evaporated under reduced pressure in order to removethe solvent therefrom, and the resulting crystal is recrystallized fromethyl acetate to give1-[4-(3-carboxypropionylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(3.61 g) as colorless needles, m.p. 192° C.

Using the suitable starting materials, the compound of the above Example253 is obtained in the same manner as in Example 392.

EXAMPLE 393

1-[4-(3-Carboxypropionylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.5 g) is dissolved in dimethylformamide (1 ml) and thereto is addeddropwise diethyl cyanophosphate (0.25 g) under ice-cooling. The mixtureis stirred at room temperature for 30 minutes and then cooled again withice. Thereto are added dropwise a solution of diethylamine (0.11 g) indimethylformamide (1 ml) and triethylamine (0.34 g). The mixture isstirred at room temperature for 16 hours. The solvent is distilled offunder reduced pressure and water is added to the resulting residue. Themixture is extracted with dichloromethane. The organic layer is washedsuccessively with diluted hydrochloric acid, water, saturated sodiumhydrogen carbonate solution, water and saturated saline solution, anddried over magnesium sulfate. The solvent is distilled off under reducedpressure and the resulting residue is purified by silica gel columnchromatography (eluent; ethyl acetate), and recrystallized fromn-hexane/ethyl acetate to give1-[4-(3-diethylaminocarbonylpropionylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.42 g) as colorless scales, m.p. 165-167° C.

Using the suitable starting materials, the compounds of the aboveExamples 255-263 are obtained in the same manner as in Example 393.

EXAMPLE 394

To a solution of1-[4-(2-chloroacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2.06 g) in dimethylformamide (5 ml) are added sodium iodide (0.90 g),potassium carbonate (1.1 g) and cyclohexylamine (0.89 g), and themixture is stirred at room temperature for 2 hours. Dimethylformamide isdistilled off under reduced pressure and water is added to the resultingresidue. The mixture is extracted with dichloromethane. The organiclayer is washed successively with water and saturated saline solution,and dried over magnesium sulfate. The solvent is distilled off underreduced pressure and the resulting residue is purified by silica gelcolumn chromatography (eluent; ethyl acetate), and recrystallized fromn-hexane/ethyl acetate to give1-[4-(2-cyclohexylaminoacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2.03 g) as white powder, m.p. 139-142° C.

Using the suitable starting materials, the compounds of the aboveExamples 271-309 and 317 are obtained in the same manner as in Example394.

EXAMPLE 395

o-Cresol (0.36 g) is dissolved in dimethylsulfoxide (4 ml) containingsodium hydroxide powder (0.18 g) and thereto is added1-[4-(2-chloroacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.03 g). The mixture is stirred at 90° C. for 7.5 hours. The reactionmixture is poured into ice-water (300 ml) and the precipitated crystalis collected by filtration, washed with water, and purified by silicagel column chromatography (eluent; n-hexane:ethyl acetate=2:1), andrecrystallized from ethyl acetate to give1-{4-[2-(2-methylphenoxy)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(546 mg) as colorless scales, m.p. 172.5-175° C.

Using the suitable starting materials, the compounds of the aboveExamples 310 and 312-316 are obtained in the same manner as in Example395.

EXAMPLE 396

A mixture of1-{4-[2-(6-bromohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(2.00 g), sodium acetate (0.36 g), sodium iodide (0.55 g) and aceticacid (20 ml) is refluxed for 1 day. The solvent is distilled off and theresulting residue is extracted with ethyl acetate. The organic layer iswashed successively with 2N aqueous sodium hydroxide solution andsaturated saline solution, and dried over magnesium sulfate. The solventis concentrated and the resulting residue is purified by silica gelcolumn chromatography (eluent; chloroform:methanol=500:1), andrecrystallized from ethanol to give1-{4-[2-(6-acetyloxyhexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(1.07 g) as white powder, m.p. 145-146° C.

Using the suitable starting materials, the compound of the above Example360 is obtained in the same manner as in Example 396.

EXAMPLE 397

A mixture of1-{4-[2-(6-bromohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g), diethylamine (0.16 ml), triethylamine (0.21 ml) andacetonitrile (20 ml) is refluxed overnight. The solvent is distilled offand the resulting residue is dissolved in chloroform, washedsuccessively with water and saturated saline solution, and dried overmagnesium sulfate. The solvent is distilled off and the resultingresidue is purified by silica gel column chromatography (eluent;chloroform:methanol=200:1→50:1) and converted into the hydrochloridethereof in methanol. The product is recrystallized from methanol/diethylether to give1-{4-[2-(6-diethylaminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride (0.42 g) as white powder, m.p. 91-95° C.

Using the suitable starting materials, the compounds of the aboveExamples 330, 332, 333, 335, 336, 339, 341, 342, 344-349, 352-355, 357and 366 are obtained in the same manner as in Example 397.

EXAMPLE 398

A mixture of1-{4-[2-(6-bromohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(4.00 g), potassium phthalimide (2.02 g) and dimethylformamide (100 ml)is stirred at 100° C. for 5 hours. The reaction mixture is filtered andthe filtrate is distilled off. The resulting residue is extracted withethyl acetate and the organic layer is washed successively with waterand saturated saline solution, and dried over magnesium sulfate. Thesolvent is distilled off and the resulting residue is purified by silicagel column chromatography (eluent; dichloromethane), and recrystallizedfrom methanol/diethyl ether to give1-{4-[2-(6-phthalimidohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(4.06 g) as white powder, m.p. 145-146.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 331, 340, 364 and 365 are obtained in the same manner as inExample 398.

EXAMPLE 399

A mixture of1-{4-[2-[6-phthalimidohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(3.75 g), hydrazine hydrate (0.44 ml) and ethanol (30 ml) is refluxedfor 3.5 hours. The precipitated crystal is collected by filtration,dried and purified by silica gel column chromatography (eluent;chloroform:methanol:aqueous ammonia=100:10:1), and recrystallized frommethanol/diethyl ether to give1-{4-[2-(6-aminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(2.52 g) as white powder, m.p. 135.5-137.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 284, 344 and 345 are obtained in the same manner as in Example399.

EXAMPLE 400

A mixture of1-{4-[2-(6-aminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g), acetic anhydride (20 ml) and two drops of conc. sulfuric acidis stirred at room temperature for 3 hours. To the reaction mixture isadded aqueous 2N aqueous sodium hydroxide solution under ice-cooling andthe mixture is extracted with chloroform. The organic layer is washedsuccessively with water and saturated saline solution, and dried overmagnesium sulfate. The solvent is distilled off and the resultingresidue is purified by silica gel column chromatography (eluent;chloroform:methanol=200:1), and recrystallized from methanol/diethylether to give1-{4-[2-(6-acetylaminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.60 g) as colorless needles, m.p. 171-172° C.

EXAMPLE 401

A mixture of1-{4-[2-(6-aminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g), benzoyl chloride (0.20 ml), triethylamine and dichloromethane(20 ml) is stirred at room temperature for 1 hour. The reaction mixtureis washed successively with water and saturated saline solution, anddried over magnesium sulfate. The solvent is concentrated and theresulting residue is recrystallized from ethanol to give1-{4-[2-(6-benzoylaminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.71 g) as white powder, m.p. 178-178.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 348 and 357 are obtained in the same manner as in Examples 400and 401.

EXAMPLE 402

A mixture of1-[4-(2-ethoxycarbonylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.00 g), aqueous ammonia (100 ml), ammonium chloride (0.3 g) andmethanol (150 ml) is heated at 100° C. for 4 hours in a sealed tube. Thesolvent is distilled off and the resulting residue is extracted withchloroform, washed successively with water and saturated salinesolution, and dried over magnesium sulfate. The solvent is concentratedand the resulting residue is purified by silica gel columnchromatography (eluent; chloroform:methanol=50:1), and recrystallizedfrom methanol/diethyl ether to give1-[4-(2-carbamoylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.43 g) as white powder, m.p. 198-199° C.

EXAMPLE 403

A mixture of1-[4-(2-chloro-4-aminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.55 g), acetic anhydride (15 ml), acetic acid (5 ml) and a drop ofsulfuric acid is stirred at room temperature for 1 hour. To the reactionmixture is added aqueous 2N aqueous sodium hydroxide solution and themixture is extracted with chloroform. The extract is washed withsaturated saline solution and dried over magnesium sulfate. The solventis concentrated and the resulting residue is recrystallized frommethanol/diethyl ether to give1-[4-(2-chloro-4-acetylaminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.28 g) as white powder, m.p. 214-243° C.

Using the suitable starting materials, the compound of the above Example44 is obtained in the same manner as in Example 403.

EXAMPLE 404

A mixture of1-[4-(1-benzyloxycarbonyl-4-piperidinylcarbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(8.00 g), 10% Pd-C (0.8 g) and ethanol (250 ml) is subjected tocatalytic hydrogenation at 50° C. under 4 atm. of hydrogen pressure for6 hours. The catalyst is removed by filtration and the filtrate isevaporated under reduced pressure. The resulting residue is extractedwith ethyl acetate and washed successively with water and saturatedsaline solution, and dried over magnesium sulfate. The solvent isdistilled off and the resulting residue is purified by silica gel columnchromatography (eluent; chloroform:methanol:ammonium hydroxide=50:10:1)to give1-{4-[4-(4-piperidinyl)benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(4.80 g), and a part (0.5 g) thereof is converted into the hydrochloridethereof in methanol. The hydrochloride is recrystallized frommethanol/diethyl ether to give1-{4-[4-(4-piperidinyl)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride (0.42 g) as white powder, m.p. 177-181.5° C.

EXAMPLE 405

Using the suitable starting materials, the following compound isobtained in the same manner as in the above Examples 1, 382 and 388.

1-[4-(4-Dimethylaminobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline,colorless amorphous

¹ H-NMR (DMSO-d₆) δ: 1.90-2.00 (2H, m), 2.82 (2H, t, J=6.5 Hz), 2.98(6H, s), 3.77 (2H, t, J=6.5 Hz), 6.70-7.30 (6H, m), 7.32 (2H, d, J=8.6Hz), 7.73 (2H, d, J=8.6 Hz), 8.00-8.20 (1H, m), 8.39 (1H, d, J=2.2 Hz),10.37 (1H, s)

Using the suitable starting materials, the following compounds areobtained in the same manner as in Example 1.

                  TABLE 2                                                         ______________________________________                                        1 #STR836##                                                                   ______________________________________                                        Example 406                                                                     Structure                                                                      -                                                                                           2  STR837##                                                                   3  STR838##                                                     -                                                                          4  STR839##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 216-218° C.                                             Form: Free                                                                    Example 407                                                                   Structure                                                                      -                                                                                           2  STR840##                                                                   3  STR841##                                                     -                                                                          5  STR842##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 181-183° C.                                             Form: Free                                                                    Example 408                                                                   Structure                                                                      -                                                                                           2  STR843##                                                                   3  STR844##                                                     -                                                                          6  STR845##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 207-208° C.                                             Form: Free                                                                    Example 409                                                                   Structure                                                                      -                                                                                           2  STR846##                                                                   3  STR847##                                                     -                                                                          7  STR848##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 213-214° C.                                             Form: Free                                                                    Example 410                                                                   Structure                                                                      -                                                                                           2  STR849##                                                                   0  STR850##                                                     -                                                                          7  STR851##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 136-138° C.                                             Form: Free                                                                    Example 411                                                                   Structure                                                                      -                                                                                           2  STR852##                                                                   0  STR853##                                                     -                                                                          6  STR854##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 130-132° C.                                             Form: Free                                                                    Example 412                                                                   Structure                                                                      -                                                                                           2  STR855##                                                                   0  STR856##                                                     -                                                                          5  STR857##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 143-145° C.                                             Form: Free                                                                    Example 413                                                                   Structure                                                                      -                                                                                           2  STR858##                                                                   0  STR859##                                                     -                                                                          4  STR860##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 171-173° C.                                             Form: Free                                                                    Example 414                                                                   Structure                                                                      -                                                                                           2  STR861##                                                                   0  STR862##                                                     -                                                                          8  STR863##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 162-164° C.                                             Form: Free                                                                    Example 415                                                                   Structure                                                                      -                                                                                           2  STR864##                                                                   9  STR865##                                                     -                                                                          7  STR866##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 49)                                                             Form: Free                                                                    Example 416                                                                   Structure                                                                      -                                                                                           2  STR867##                                                                   9  STR868##                                                     -                                                                          4  STR869##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 50)                                                             Form: Free                                                                    Example 417                                                                   Structure                                                                      -                                                                                           2  STR870##                                                                   4  STR871##                                                     -                                                                          6  STR872##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 51)                                                             Form: Free                                                                    Example 418                                                                   Structure                                                                      -                                                                                           2  STR873##                                                                   0  STR874##                                                     -                                                                          4  STR875##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 228.5-230° C.                                           Form: Free                                                                    Example 419                                                                   Structure                                                                      -                                                                                           2  STR876##                                                                   1  STR877##                                                     -                                                                          4  STR878##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting point: 205.5-206.5° C.                                         Form: Free                                                                    Example 420                                                                   Structure                                                                      -                                                                                           2  STR879##                                                                   1  STR880##                                                     -                                                                          2  STR881##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting point: 210-212° C.                                             Form: Free                                                                    Example 421                                                                   Structure                                                                      -                                                                                           2  STR882##                                                                   3  STR883##                                                     -                                                                          6  STR884##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 166-167° C.                                             Form: Free                                                                    Example 422                                                                   Structure                                                                      -                                                                                           2  STR885##                                                                   3  STR886##                                                     -                                                                          7  STR887##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 191.5-192.5° C.                                         Form: Free                                                                    Example 423                                                                   Structure                                                                      -                                                                                           2  STR888##                                                                   3  STR889##                                                     -                                                                          4  STR890##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 209-210° C.                                             Form: Free                                                                    Example 424                                                                   Structure                                                                      -                                                                                           2  STR891##                                                                   3  STR892##                                                     -                                                                          5  STR893##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 52)                                                             Form: Free                                                                    Example 425                                                                   Structure                                                                      -                                                                                           2  STR894##                                                                   3  STR895##                                                     -                                                                          8  STR896##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 148-149° C.                                             Form: Free                                                                    Example 426                                                                   Structure                                                                      -                                                                                           2  STR897##                                                                   4  STR898##                                                     -                                                                          6  STR899##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 157-158° C.                                             Form: Free                                                                    Example 427                                                                   Structure                                                                      -                                                                                           2  STR900##                                                                   4  STR901##                                                     -                                                                          7  STR902##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 194.5-195.5° C.                                         Form: Free                                                                    Example 428                                                                   Structure                                                                      -                                                                                           2  STR903##                                                                   4  STR904##                                                     -                                                                          4  STR905##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 179.5-180.5° C.                                         Form: Free                                                                    Example 429                                                                   Structure                                                                      -                                                                                           2  STR906##                                                                   4  STR907##                                                     -                                                                          5  STR908##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 190-191° C.                                             Form: Free                                                                    Example 430                                                                   Structure                                                                      -                                                                                           2  STR909##                                                                   4  STR910##                                                     -                                                                          8  STR911##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 159-160° C.                                             Form: Free                                                                    Example 431                                                                   Structure                                                                      -                                                                                           2  STR912##                                                                   5  STR913##                                                     -                                                                          6  STR914##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 53)                                                             Form: Hydrochloride                                                           Example 432                                                                   Structure                                                                      -                                                                                           2  STR915##                                                                   5  STR916##                                                     -                                                                          7  STR917##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 155-156° C.                                             Form: Free                                                                    Example 433                                                                   Structure                                                                      -                                                                                           2  STR918##                                                                   5  STR919##                                                     -                                                                          4  STR920##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 54)                                                             Form: Free                                                                    Example 434                                                                   Structure                                                                      -                                                                                           2  STR921##                                                                   5  STR922##                                                     -                                                                          5  STR923##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 55)                                                             Form: Free                                                                    Example 435                                                                   Structure                                                                      -                                                                                           2  STR924##                                                                   5  STR925##                                                     -                                                                          8  STR926##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 175-177° C.                                             Form: Free                                                                    Example 436                                                                   Structure                                                                      -                                                                                           2  STR927##                                                                   6  STR928##                                                     -                                                                          6  STR929##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 56)                                                             Form: Free                                                                    Example 437                                                                   Structure                                                                      -                                                                                           2  STR930##                                                                   6  STR931##                                                     -                                                                          7  STR932##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 57)                                                             Form: Free                                                                    Example 438                                                                   Structure                                                                      -                                                                                           2  STR933##                                                                   7  STR934##                                                     -                                                                          6  STR935##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 219-220° C.                                             Form: Free                                                                    Example 439                                                                   Structure                                                                      -                                                                                           2  STR936##                                                                   7  STR937##                                                     -                                                                          7  STR938##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 215-218° C.                                             Form: Free                                                                    Example 440                                                                   Structure                                                                      -                                                                                           2  STR939##                                                                   8  STR940##                                                     -                                                                          9  STR941##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 128.5-129.5° C.                                         Form: Free                                                                    Example 441                                                                   Structure                                                                      -                                                                                           2  STR942##                                                                   8  STR943##                                                     -                                                                          0  STR944##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 58)                                                             Form: Free                                                                    Example 442                                                                   Structure                                                                      -                                                                                           2  STR945##                                                                   8  STR946##                                                     -                                                                             -                                                                          1  STR947##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 153-154° C.                                             Form: Free                                                                    Example 443                                                                   Structure                                                                      -                                                                                           2  STR948##                                                                   8  STR949##                                                     -                                                                          2  STR950##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 150-153° C.                                             Form: Free                                                                    Example 444                                                                   Structure                                                                      -                                                                                           2  STR951##                                                                   8  STR952##                                                     -                                                                          3  STR953##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 139-141° C.                                             Form: Free                                                                    Example 445                                                                   Structure                                                                      -                                                                                           2  STR954##                                                                   8  STR955##                                                     -                                                                          4  STR956##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 59)                                                             Form: Free                                                                    Example 446                                                                   Structure                                                                      -                                                                                           2  STR957##                                                                   8  STR958##                                                     -                                                                          9  STR959##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 60)                                                             Form: Free                                                                    Example 447                                                                   Structure                                                                      -                                                                                           2  STR960##                                                                   8  STR961##                                                     -                                                                          5  STR962##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 61)                                                             Form: Free                                                                    Example 448                                                                   Structure                                                                      -                                                                                           2  STR963##                                                                   8  STR964##                                                     -                                                                          6  STR965##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 62)                                                             Form: Free                                                                    Example 449                                                                   Structure                                                                      -                                                                                           2  STR966##                                                                   1  STR967##                                                     -                                                                          8  STR968##                                                                      - Crystalline form: Colorless amorphous                                      NMR analysis: 63)                                                             Form: Free                                                                    Example 450                                                                   Structure                                                                      -                                                                                           2  STR969##                                                                   7  STR970##                                                     -                                                                          9  STR971##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 172.5-173.5° C.                                         Form: Free                                                                    Example 451                                                                   Structure                                                                      -                                                                                           2  STR972##                                                                   7  STR973##                                                     -                                                                          0  STR974##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 122.5-123° C.                                           Form: Free                                                                    Example 452                                                                   Structure                                                                      -                                                                                           2  STR975##                                                                   7  STR976##                                                     -                                                                          1  STR977##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 198-199.5° C.                                           Form: Free                                                                    Example 453                                                                   Structure                                                                      -                                                                                           2  STR978##                                                                   7  STR979##                                                     -                                                                          2  STR980##                                                                      - Crystalline from: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 118-119.5° C.                                           Form: Hydrochloride                                                           Example 454                                                                   Structure                                                                      -                                                                                           2  STR981##                                                                   7  STR982##                                                     -                                                                          3  STR983##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 163-165° C.                                             Form: Dihydrochloride                                                         Example 455                                                                   Structure                                                                      -                                                                                           2  STR984##                                                                   7  STR985##                                                     -                                                                          4  STR986##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 246-248° C.                                             Form: Hydrochloride                                                           Example 456                                                                   Structure                                                                      -                                                                                           2  STR987##                                                                   7  STR988##                                                     -                                                                          5  STR989##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Chloroform/ethanol                                 Melting Point: 204-205° C.                                             Form: Free                                                                    Example 457                                                                   Structure                                                                      -                                                                                           2  STR990##                                                                   7  STR991##                                                     -                                                                          6  STR992##                                                                      - Crystalline form: Colorless prisms                                         Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 127-128° C.                                             Form: Hydrochloride                                                           Example 458                                                                   Structure                                                                      -                                                                                           2  STR993##                                                                   7  STR994##                                                     -                                                                          7  STR995##                                                                      - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 220-221° C.                                             Form: Free                                                                    Example 459                                                                   Structure                                                                      -                                                                                           2  STR996##                                                                   7  STR997##                                                     -                                                                          8  STR998##                                                                      - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 190-192° C.                                             Form: Free                                                                    Example 460                                                                   Structure                                                                      -                                                                                           2  STR999##                                                                   7  STR1000##                                                    -                                                                          9  STR1001##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 189-191° C.                                             Form: Hydrochloride                                                           Example 461                                                                   Structure                                                                      -                                                                                           2  STR1002##                                                                  7  STR1003##                                                    -                                                                          0  STR1004##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 173-174° C.                                             Form: Free                                                                    Example 462                                                                   Structure                                                                      -                                                                                           2  STR1005##                                                                  7  STR1006##                                                    -                                                                          1  STR1007##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethanol                            Melting Point: 129-130° C.                                             Form: Free                                                                    Example 463                                                                   Structure                                                                      -                                                                                           2  STR1008##                                                                  7  STR1009##                                                    -                                                                          2  STR1010##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 130-133° C.                                             Form: Hydrochloride                                                           Example 464                                                                   Structure                                                                      -                                                                                           2  STR1011##                                                                  7  STR1012##                                                    -                                                                          3  STR1013##                                                                     - Crystalline form: Light yellow powder                                      Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 170.5-172° C.                                           Form: Hydrochloride                                                           Example 465                                                                   Structure                                                                      -                                                                                           2  STR1014##                                                                  7  STR1015##                                                    -                                                                          4  STR1016##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 126-131° C.                                             Form: Hydrochloride                                                           Example 466                                                                   Structure                                                                      -                                                                                           2  STR1017##                                                                  7  STR1018##                                                    -                                                                          5  STR1019##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 182-185° C.                                             Form: Dihydrochloride                                                         Example 467                                                                   Structure                                                                      -                                                                                           2  STR1020##                                                                  7  STR1021##                                                    -                                                                          6  STR1022##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 116-121° C.                                             Form: Hydrochloride                                                           Example 468                                                                   Structure                                                                      -                                                                                           2  STR1023##                                                                  7  STR1024##                                                    -                                                                          7  STR1025##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 178-182.5° C.                                           Form: Free                                                                    Example 469                                                                   Structure                                                                      -                                                                                           2  STR1026##                                                                  7  STR1027##                                                    -                                                                          8  STR1028##                                                                     - Crystalline form: Colorless particles                                      Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 185-187° C.                                             Form: Free                                                                    Example 470                                                                   Structure                                                                      -                                                                                           2  STR1029##                                                                  7  STR1030##                                                    -                                                                          9  STR1031##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 215-217° C.                                             Form: Free                                                                    Example 471                                                                   Structure                                                                      -                                                                                           2  STR1032##                                                                  7  STR1033##                                                    -                                                                          0  STR1034##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 176-178° C.                                             Form: Free                                                                    Example 472                                                                   Structure                                                                      -                                                                                           2  STR1035##                                                                  7  STR1036##                                                    -                                                                          1  STR1037##                                                                     - Crystalline form: Light yellow powder                                      Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 194.5-197° C.                                           Form: Free                                                                    Example 473                                                                   Structure                                                                      -                                                                                           2  STR1038##                                                                  7  STR1039##                                                    -                                                                          2  STR1040##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 161.5-165.5° C.                                         Form: Hydrochloride                                                           Example 474                                                                   Structure                                                                      -                                                                                           2  STR1041##                                                                  7  STR1042##                                                    -                                                                          3  STR1043##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point 152-153° C.                                              Form: Free                                                                    Example 475                                                                   Structure                                                                      -                                                                                           2  STR1044##                                                                  7  STR1045##                                                    -                                                                          4  STR1046##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 147-148° C.                                             Form: Free                                                                    Example 476                                                                   Structure                                                                      -                                                                                           2  STR1047##                                                                  7  STR1048##                                                    -                                                                          5  STR1049##                                                                     - Crystalline form: Light yellow powder                                      Recrystallization solvent: Ethyl acetate                                      Melting Point: 25-217° C.                                              Form: Free                                                                    Example 477                                                                   Structure                                                                      -                                                                                           2  STR1050##                                                                  7  STR1051##                                                    -                                                                          6  STR1052##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 64)                                                             Form: Free                                                                    Example 478                                                                   Structure                                                                      -                                                                                           2  STR1053##                                                                  7  STR1054##                                                    -                                                                          7  STR1055##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 180-181° C.                                             Form: Free                                                                    Example 479                                                                   Structure                                                                      -                                                                                           2  STR1056##                                                                  7  STR1057##                                                    -                                                                          8  STR1058##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 65)                                                             Form: Free                                                                    Example 480                                                                   Structure                                                                      -                                                                                           2  STR1059##                                                                  7  STR1060##                                                    -                                                                          9  STR1061##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 66)                                                             Form: Free                                                                    Example 481                                                                   Structure                                                                      -                                                                                           2  STR1062##                                                                  7  STR1063##                                                    -                                                                          0  STR1064##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 67)                                                             Form: Free                                                                    Example 482                                                                   Structure                                                                      -                                                                                           2  STR1065##                                                                  7  STR1066##                                                    -                                                                          1  STR1067##                                                                     - Crystalline form: Colorless scales                                         Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 165-167° C.                                             Form: Free                                                                    Example 483                                                                   Structure                                                                      -                                                                                           2  STR1068##                                                                  7  STR1069##                                                    -                                                                          2  STR1070##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 68)                                                             Form: Free                                                                    Example 484                                                                   Structure                                                                      -                                                                                           2  STR1071##                                                                  7  STR1072##                                                    -                                                                          3  STR1073##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 69)                                                             Form: Free                                                                    Example 485                                                                   Structure                                                                      -                                                                                           2  STR1074##                                                                  7  STR1075##                                                    -                                                                          4  STR1076##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 70)                                                             Form: Free                                                                    Example 486                                                                   Structure                                                                      -                                                                                           2  STR1077##                                                                  7  STR1078##                                                    -                                                                          5  STR1079##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 71)                                                             Form: Free                                                                    Example 487                                                                   Structure                                                                      -                                                                                           2  STR1080##                                                                  7  STR1081##                                                    -                                                                          6  STR1082##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 72)                                                             Form: Free                                                                    Example 488                                                                   Structure                                                                      -                                                                                           2  STR1083##                                                                  7  STR1084##                                                    -                                                                          7  STR1085##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 73)                                                             Form: Free                                                                    Example 489                                                                   Structure                                                                      -                                                                                           2  STR1086##                                                                  7  STR1087##                                                    -                                                                          8  STR1088##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 74)                                                             Form: Free                                                                    Example 490                                                                   Structure                                                                      -                                                                                           2  STR1089##                                                                  7  STR1090##                                                    -                                                                          9  STR1091##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 182-182.5° C.                                           Form: Free                                                                    Example 491                                                                   Structure                                                                      -                                                                                           2  STR1092##                                                                  7  STR1093##                                                    -                                                                          0  STR1094##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 244-245° C.                                             Form: Free                                                                    Example 492                                                                   Structure                                                                      -                                                                                           2  STR1095##                                                                  7  STR1096##                                                    -                                                                          1  STR1097##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 220-221.5° C.                                           Form: Free                                                                    Example 493                                                                   Structure                                                                                    2  STR1098##                                                                  2  STR1099##                                                    -                                                                          3  STR1100##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 75)                                                             Form: Free                                                                    Example 494                                                                   Structure                                                                                    2  STR1101##                                                                  2  STR1102##                                                    -                                                                          3  STR1103##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 76)                                                             Form: Free                                                                    Example 495                                                                   Structure                                                                      -                                                                                           2  STR1104##                                                                  7  STR1105##                                                    -                                                                          4  STR1106##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 171-172° C.                                             Form: Free                                                                    Example 496                                                                   Structure                                                                      -                                                                                           2  STR1107##                                                                  7  STR1108##                                                    -                                                                          5  STR1109##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 178-178.5° C.                                           Form: Free                                                                    Example 497                                                                   Structure                                                                      -                                                                                           2  STR1110##                                                                  7  STR1111##                                                    -                                                                          6  STR1112##                                                                     - Example 498                                                                Structure                                                                      -                                                                                           2  STR1113##                                                                  7  STR1114##                                                    -                                                                          7  STR1115##                                                                     - Example 499                                                                Structure                                                                      -                                                                                           2  STR1116##                                                                  7  STR1117##                                                    -                                                                          8  STR1118##                                                                     - Example 500                                                                Structure                                                                      -                                                                                           2  STR1119##                                                                  7  STR1120##                                                    -                                                                          9  STR1121##                                                                     - Example 501                                                                Structure                                                                      -                                                                                           2  STR1122##                                                                  7  STR1123##                                                    -                                                                          0  STR1124##                                                                     - Example 502                                                                Structure                                                                      -                                                                                           2  STR1125##                                                                  7  STR1126##                                                    -                                                                          1  STR1127##                                                                     - Example 503                                                                Structure                                                                      -                                                                                           2  STR1128##                                                                  7  STR1129##                                                    -                                                                          2  STR1130##                                                                     - Example 504                                                                Structure                                                                      -                                                                                           2  STR1131##                                                                  7  STR1132##                                                    -                                                                          3  STR1133##                                                                     - Crystalline form: Light yellow scales                                      Recrystallization solvent: Ethanol/water                                      Melting Point: 129-131° C.                                             Form: Free                                                                    Example 505                                                                   Structure                                                                      -                                                                                           2  STR1134##                                                                  7  STR1135##                                                    -                                                                          4  STR1136##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 199-201° C.                                             Form: Free                                                                    Example 506                                                                   Structure                                                                      -                                                                                           2  STR1137##                                                                  5  STR1138##                                                    -                                                                          6  STR1139##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 77)                                                             Form: Free                                                                    Example 507                                                                   Structure                                                                      -                                                                                           2  STR1140##                                                                  5  STR1141##                                                    -                                                                          8  STR1142##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 187.5-189° C.                                           Form: Free                                                                    Example 508                                                                   Structure                                                                      -                                                                                           2  STR1143##                                                                  6  STR1144##                                                    -                                                                          7  STR1145##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 161-164° C.                                             Form: Free                                                                    Example 509                                                                   Structure                                                                      -                                                                                           2  STR1146##                                                                  6  STR1147##                                                    -                                                                          4  STR1148##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 242-243° C.                                             Form: Free                                                                    Example 510                                                                   Structure                                                                      -                                                                                           2  STR1149##                                                                  1  STR1150##                                                    -                                                                          R.sup.3 : 4-NHCOCH.sub.2 Cl                                                     Crystalline form: White powder                                                Recrystallization solvent: Dichloroethane/diethyl ether                       Melting Point: 186-188° C.                                             Form: Free                                                                    Example 511                                                                   Structure                                                                      -                                                                                           2  STR1151##                                                                  7  STR1152##                                                    -                                                                          7  STR1153##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 78)                                                             Form: Free                                                                    Example 512                                                                   Structure                                                                      -                                                                                           2  STR1154##                                                                  7  STR1155##                                                    -                                                                          8  STR1156##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 79)                                                             Form: Free                                                                  ______________________________________                                          49)   .sup.1 H-NMR(CDCl.sub.3)δ; 1.11(3H, t, J=7.1Hz), 1.90-2.25                (2H, m), 2.29(3H, s), 2.55(2H, q, J=7.1Hz),                            3.62-3.90(2H, m), 4.00-4.20(1H, m), 6.63(1H, d,                               J=7.9Hz), 6.85-7.10(2H, m), 7.25-7.80(9H, m),                                 8.25(1H, brs)                                                                50) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10(3H, t, J=7.1Hz), 1.90-2.20                  (2H, m), 2.28(3H, s), 3.60-3.90(2H, m), 3.95-4.20                      (1H, m), 6.62(1H, d, J=7.9Hz), 6.80-7.10(2H, m),                              7.20(2H, d, J=8.6Hz), 7.31-7.55(4H, m), 7.80                                  (2H, d, J=1.9Hz), 9.05(1H, brs)                                              51) .sup.1 H-NMR(CDCl.sub.3)δ; 1.80-2.05(1H, m), 2.15-2.50(1H,                  m), 2.34(6H, s), 2.51(3H, s), 3.48-3.62(1H, m),                        3.72(3H, s), 3.70-3.85(1H, m), 4.00-4.22(1H, m),                              6.64(1H, d, J=7.8Hz), 6.84-7.58(9H, m), 8.16                                  (1H, brs), 8.40(1H, d, J=8.7Hz)                                              52) .sup.1 H-NMR(CDCl.sub.3)δ; 1.16(3H, t, J=7.1Hz), 2.40-2.70                  (2H, m), 2.90-3.30(3H, m), 3.80-4.20(2H, m),                           4.80-5.00(1H, m), 6.60-6.80(1H, m), 7.00-7.70                                 (10H, m), 8.24(1H, s)                                                        53) .sup.1 H-NMR(DMSO-d.sub.6)δ; 1.0-2.5(10H, m), 2.34(3H, s),                  3.30-3.80(4H, m), 4.50-5.30(3H, m), 6.70-7.00                          (1H, m), 7.10-7.80(11H, m), 10.43(1H, s), 10.5-                               12.0(1H, br)                                                                 54) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10-2.10(10H, m), 2.40-2.70                     (1H, m), 2.80-3.20(3H, m), 3.92(2H, s), 4.90-5.20                      (1H, m), 6.50-6.70(1H, m), 6.80-7.60(8H, m), 7.75                             (2H, s), 8.73(1H, s)                                                         55) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10-2.20(10H, m), 2.40-2.70                     (1H, m), 2.90-3.30(3H, m), 3.93(2H, s), 4.90-5.20                      (1H, m), 6.62(1H, d, J=7.6Hz), 6.90-7.70(10H,                                 m), 8.29(1H, s)                                                              56) .sup.1 H-NMR(CDCl.sub.3)δ; 1.50-2.10(2H, m), 2.38(6H, s),                   2.30-2.70(1H, m), 2.70-3.00(2H, m), 3.45(1H, d,                        J=13Hz), 3.81(1H, d, J=14Hz), 4.70-5.00(1H, m),                               7.0-7.50(12H, m), 8.23(1H, s)                                                57) .sup.1 H-NMR(CDCl.sub.3)δ; 1.50-2.10(2H, m), 2.42(3H, s),                   2.40-2.70(1H, m), 2.80-3.00(2H, m), 3.52(1H, d,                        J=13Hz), 3.85(1H, d, J=13Hz), 4.70-5.00(1H, m),                               7.00-7.70(12H, m), 8.54(1H, s)                                               58) .sup.1 H-NMR(CDCl.sub.3)δ; 2.43(3H, s), 2.47(3H, s), 3.00-                  3.30(3H, m), 3.76(1H, d, J=14Hz), 4.06(1H, d,                          J=14Hz), 4.90-5.20(1H, m), 6.50-6.80(3H, m),                                  6.90-7.50(6H, m), 7.70-8.00(2H, m), 8.48(1H, d,                               J=8Hz), 10.58(1H, s)                                                         59) .sup.1 H-NMR(CDCl.sub.3)δ; 2.41(3H, s), 2.44(3H, s), 2.90-                  3.20(3H, m), 3.74(1H, d, J=13Hz), 4.07(1H, d,                          J=14Hz), 4.80-5.00(1H, m), 6.67(1H, d, J=7Hz),                                6.76(1H, d, J=7Hz), 7.00-7.50(8H, m), 7.55(1H,                                s), 7.70-7.90(2H, m)                                                         60) .sup.1 H-NMR(CDCl.sub.3)δ; 2.41)3H, s), 2.80-3.20(3H, m),                   3.73(1H, d, J=13Hz), 4.03(1H, d, J=14Hz), 6.66                         (2H, d, J=7.6Hz), 6.90-8.00(10H, m), 8.57(1H, s)                             61) .sup.1 H-NMR(CDCl.sub.3)δ; 2.40(3H, s), 2.90-3.20(3H, m),                   3.73(1H, d, J=13Hz), 4.07(1H, d, J=13Hz), 4.70-                        5.00(1H, m), 6.60-6.80(2H, m), 6.90-8.00(10H,                                 m), 8.54(1H, s)                                                              62) .sup.1 H-NMR(CDCl.sub.3)δ; 2.41(3H, s), 2.90-3.20(3H, m),                   3.75(1H, d, J=14Hz), 4.08(1H, d, J=14Hz), 4.80-                        5.00(1H, m), 6.67(1H, d, J=7.6Hz), 6.82(1H, d,                                J=7.6Hz), 6.90-7.90(10H, m), 8.08(1H, s)                                     63) .sup.1 H-NMR(CDCl.sub.3)δ; 1.23(3H, t, J=7Hz), 1.40-1.70                    (1H, m), 1.90-2.20(3H, m), 2.70-3.30(3H, m),                           3.40-3.60(5H, m), 3.91(2H, s), 5.00-5.20(1H, m),                              6.60-7.40(11H, m), 8.12(1H, d, J=8Hz), 8.99(1H, s)                           64) .sup.1 H-NMR(CDCl.sub.3)δ; 1.35-1.70(1H, m), 1.80-2.20(3H,                  m), 2.25-2.35(1H, m), 2.65-3.20(3H, m), 4.01(2H,                       s), 4.05-4.17(2H, m), 4.90-5.10(1H, m), 6.61(1H,                              d, J=7.5Hz), 6.75-7.50(12H, m), 8.44(1H, brs)                                65) .sup.1 H-NMR(CDCl.sub.3)δ; 1.13(3H, t, J=7.0Hz), 1.30-1.65                  (4H, m), 1.80-2.20(3H, m), 2.28(3H, s), 2.65-3.40                      (5H, m), 4.90-5.10(1H, m), 6.63(1H, d, J=7.8Hz),                              6.75-7.00(3H, m), 7.00-7.45(8H, m), 8.85(1H, brs)                            66) .sup.1 H-NMR(CDCl.sub.3)δ; 0.88(3H, t, J=7.4Hz), 1.16(3H,                   t, J=7.0Hz), 1.35-2.20(6H, m), 2.27(3H, s),                            2.60-3.20(3H, m), 3.20-3.45(2H, m), 3.85-4.10                                 (1H, m), 4.90-5.10(1H, m), 6.63(1H, d, J=7.4Hz),                              6.67(2H, d, J=8.5Hz), 6.92(1H, t, J=8.0Hz),                                   7.00-7.45(8H, m), 8.85(1H, brs)                                              67) .sup.1 H-NMR(CDCl.sub.3)δ; 1.17(3H, t, J=7.0Hz), 1.35-1.65                  (4H, m), 2.60-3.45(5H, m), 4.20(2H, q, J=7.0Hz),                       4.90-5.10(1H, m), 6.63(1H, d, J=7.6Hz), 6.80-                                 7.45(12H, m), 8.66(1H, brs)                                                  68) .sup.1 H-NMR(CDCl.sub.3)δ; 0.96(6H, d, J=6.6Hz), 1.35-1.65                  (1H, m), 1.80-2.25(4H, m), 2.65-3.15(3H, m), 3.19                      (2H, d, J=7.3Hz), 3.99(2H, s), 4.90-5.10(1H, m),                              6.60(1H, d, J=7.8Hz), 6.75-7.05(4H, m), 7.05-                                 7.40(8H, m), 8.15(1H, brs)                                                   69) .sup.1 H-NMR(CDCl.sub.3)δ; 1.19(3H, t, J=7.0Hz), 1.35-1.65                  (1H, m), 1.80-2.25(3H, m), 2.70-3.20(3H, m), 3.44                      (2H, q, J=7.0Hz), 3.77(3H, s), 3.87(2H, s),                                   4.90-5.10(1H, m), 6.25-6.50(3H, m), 6.67(1H, d,                               J=7.5Hz), 6.85-7.45(8H, m), 8.29(1H, brs)                                    70) .sup.1 H-NMR(CDCl.sub.3)δ; 1.05(3H, t, J=7.1Hz), 1.35-1.65                  (1H, m), 1.85-2.25(3H, m), 2.65-3.30(5H, m), 3.74                      (2H, s), 4.95-5.15(1H, m), 6.63(1H, d, J=7.5Hz),                              6.80-7.55(11H, m), 9.51(1H, brs)                                             71) .sup.1 H-NMR(CDCl.sub.3)δ; 1.30-1.65(1H, m), 1.80-2.30(3H,                  m), 2.65-3.15(3H, m), 3.75(2H, s), 3.74(2H, s),                        4.95-5.10(1H, m), 6.45-6.70(3H, m), 6.88(1H, t,                               J=6.8Hz), 7.00-7.45(8H, m), 8.74(1H, brs)                                    72) .sup.1 H-NMR(CDCl.sub.3)δ; 1.30-1.70(1H, m), 1.75-2.25(6H,                  m), 2.65-3.15(3H, m), 3.78(2H, d, J=5.4Hz), 4.28                       (2H, d, J=5.5Hz), 4.53(1H, brs), 4.90-5.10(1H,                                m), 5.89(1H, brs), 6.50-6.70(3H, m), 6.89(1H, t,                              J=7.5Hz), 7.00-7.40(8H, m), 8.61(1H, brs)                                    73) .sup.1 H-NMR(CDCl.sub.3)δ; 1.35-1.65(1H, m), 1.70-2.20(8H,                  m), 2.65-3.20(3H, m), 3.25-3.55(4H, m), 3.88(2H,                       s), 4.90-5.10(1H, m), 5.79(1H, brs), 6.55-7.40                                (13H, m), 8.37(1H, brs)                                                      74) .sup.1 H-NMR(CDCl.sub.3)δ; 1.35-2.00(8H, m), 2.65-3.20(3H,                  m), 3.30-3.35(2H, m), 3.60-3.85(2H, m), 3.90(2H,                       s), 4.95-5.15(1H, m), 6.55-7.00(5H, m), 7.00-7.40                             (8H, m), 7.65-7.90(4H, m), 8.22(1H, brs)                                     75) .sup.1 H-NMR(CDCl.sub.3)δ; 1.16(3H, t, J=7.0Hz), 2.39(3H,                   s), 2.80-3.20(3H, m), 3.44(2H, q, J=7.0Hz),                            3.65-4.20(4H, m), 4.80-5.05(1H, m), 6.50-7.45                                 (13H, m), 8.50(1H, brs)                                                      76) .sup.1 H-NMR(CDCl.sub.3)δ; 1.23(3H, t, J=7.0Hz), 2.41(3H,                   s), 2.75-3.20(3H, m), 3.40-3.60(5H, m), 3.65-3.90                      (1H, m), 3.92(2H, s), 3.90-4.20(1H, m), 4.85-5.10                             (1H, m), 6.65-7.45(11H, m), 8.13(1H, d, J=8.4                                 Hz), 9.01(1H, brs)                                                           77) .sup.1 H-NMR(CDCl.sub.3)δ; 1.80-1.95(1H, m), 2.20-2.70                      (10H, m), 3.50-3.60(1H, m), 3.63-3.80(1H, m),                          4.00-4.15(1H, m), 6.60(1H, d, J=7.6Hz), 6.92                                  (1H, t, J=7.6Hz), 7.02(1H, t, J=6.3Hz), 7.20-                                 7.65(9H, m), 7.87(1H, brs)                                                   78) .sup.1 H-NMR(CDCl.sub.3)δ; 1.40-1.62(1H, m), 1.84-2.22(3H,                  m), 2.65-3.19(3H, m), 3.97(2H, t, J=4.9Hz), 4.43                       (2H, t, J=4.9Hz), 4.95-5.18(1H, m), 6.60-6.77                                 (1H, m), 6.85-7.02(2H, m), 7.02-7.30(5H, m),                                  7.40-7.68(3H, m), 8.20-8.32(1H, m), 9.62-9.81                                 (1H, m)                                                                      79) .sup.1 H-NMR(CDCl.sub.3)δ; 1.38-1.65(1H, m), 1.84-2.21(3H,                  m), 2.64-3.15(3H, m), 3.81(2H, t, J=5.7Hz), 4.25                       (2H, t, J=5.7Hz), 4.90-5.13(1H, m), 6.58-6.71                                 (1H, m), 6.82-7.00(1H, m), 7.00-7.52(10H, m),                                 8.11(1H, brs)                                                              ______________________________________                                    

EXAMPLE 513

To a solution of 1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(1.06 g) in dichloromethane (80 ml) is added o-methylphenyl isocyanate(0.66 g) under ice-cooling. The mixture is stirred at room temperaturefor 4 hours. After completion of the reaction, the solvent isconcentrated under reduced pressure and the resulting residue ispurified by silica gel column chromatography (eluent; n-hexane:ethylacetate=1:1), and recrystallized from ethyl acetate to give1-[4-(2-methylanilinocarbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.97 g) as white powder, m.p. 182-182.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 491-492 are obtained in the same manner as in Example 513.

EXAMPLE 514

A mixture of 1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.50g), phenylsulfonyl chloride (0.29 ml), triethylamine (0.32 ml) anddichloromethane (30 ml) is stirred at room temperature overnight. Thereaction mixture is washed successively with water and saturated salinesolution, and dried over magnesium sulfate. The solvent is distilled offand the resulting residue is purified by silica gel columnchromatography (eluent; chloroform), and recrystallized frommethanol/diethyl ether to give1-(4-phenylsulfonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.27g) as colorless prisms, m.p. 178-182.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 469-471, 498, 502 and 503 are obtained in the same manner as inExample 514.

EXAMPLE 515

To a solution of1-[4-(4-piperidinylcarbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.70 9) in dimethylformamide (20 ml) is added 60% sodium hydridedispersion in mineral oil (82 mg) and the mixture is stirred at roomtemperature for 30 minutes. Thereto is added methyl iodide (0.14 ml) andthe mixture is stirred ar room temperature overnight. The solvent isdistilled off and the resulting residue is extracted with chloroform,and washed successively with water and saturated saline solution, anddried over magnesium sulfate. The solvent is distilled off and theresulting residue is purified by silica gel column chromatography(eluent; chloroform:methanol=10:1), and recrystallized frommethanol/n-hexane to give1-{4-[N-(1-methyl-4-piperidinylcarbonyl)-N-methylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.03 g) as light yellow powder, m.p. 194.5-197° C.

Using the suitable starting materials, the compounds of the aboveExamples 497 and 501 are obtained in the same manner as in Example 515.

EXAMPLE 516

6-Fluoro-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline (0.15 g) isdissolved in dichloromethane (10 ml) and thereto is added triethylamine(0.31 ml). To the mixture is added dropwise a solution of3,5-dichlorobenzoyl chloride (0.14 g) in dichloromethane (2.0 ml) underice-cooling, and the mixture is stirred for 30 minutes underice-cooling, and further, at room temperature for 1 hour. To the mixtureare added triethylamine (0.31 ml) and 3,5-dichlorobenzoyl chloride (0.14ml). The mixture is stirred at room temperature for 4 hours. Thereaction mixture is washed with water, and dried over magnesium sulfate.The solvent is distilled off and the resulting residue is purified bysilica gel column chromatography (eluent; ethylacetate:n-hexane=1:5→1:4), and recrystallized from ethylacetate/n-hexane to give6-fluoro-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.12 g) and6-fluoro-1-{4-[bis-(3,5-dichlorobenzoyl)amino]benzoyl}-1,2,3,4-tetrahydroquinoline.

The former: White powder, m.p. 205.5-206.5° C.

The latter: White powder, m.p. 210.5-212° C.

EXAMPLE 517

Using the suitable starting materials, the compounds of the aboveExamples 450 and 504 are obtained in the same manner as in Example 378.

EXAMPLE 518

Using the suitable starting materials, the compounds of the aboveExamples 450-467, 495, 496, 499, 500, 511 and 512 are obtained in thesame manner as in Example 380.

EXAMPLE 519

Using the suitable starting materials, the compounds of the aboveExamples 449, 474-489, 493 and 494 are obtained in the same manner as inExample 394.

EXAMPLE 520

Using the suitable starting materials, the compounds of the aboveExamples 453, 455, 457, 459, 460, 463-467, 495, 496 and 499 are obtainedin the same manner as in Example 397.

EXAMPLE 521

Using the suitable starting materials, the compound of the above Example461 is obtained in the same manner as in Example 396.

EXAMPLE 522

Using the suitable starting materials, the compound of the above Example456 is obtained in the same manner as in Example 398.

EXAMPLE 523

Using the suitable starting materials, the compound of the above Example459 is obtained in the same manner as in Example 399.

EXAMPLE 524

Using the suitable starting materials, the compounds of the aboveExamples 495 and 496 are obtained in the same manner as in Examples 400and 401.

EXAMPLE 525

Using the suitable starting materials, the compound of the above Example458 is obtained in the same manner as in Example 402.

Using the suitable starting materials, the compounds of the followingTable 3 are obtained in the same manner as in Examples 1 and 382.

                  TABLE 3                                                         ______________________________________                                        1 #STR1157##                                                                  ______________________________________                                            Example 527                                                                 Structure                                                                   2  STR1158##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          3  STR1159##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 225-226° C.                                             Form: Free                                                                    Example 528                                                                   Structure                                                                      -                                                                          4  STR1160##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1161##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 142.5-145° C.                                           Form: Free                                                                    Example 529                                                                   Structure                                                                      -                                                                          6  STR1162##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          7  STR1163##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 213-215° C.                                             Form: Free                                                                    Example 530                                                                   Structure                                                                      -                                                                          8  STR1164##                                                                     - R.sup.2 : 3-CH.sub.3                                                        -                                                                          9  STR1165##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 167-167.5° C.                                           Form: Free                                                                    Example 531                                                                   Structure                                                                      -                                                                          0  STR1166##                                                                     - R.sup.2 : 3-CH.sub.3                                                        -                                                                          1  STR1167##                                                                     - Crystalline form: Colorless scales                                         Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 217-221° C.                                             Form: Free                                                                    Example 532                                                                   Structure                                                                      -                                                                          2  STR1168##                                                                     - R.sup.2 : 3-CH.sub.3                                                        -                                                                          3  STR1169##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 182-184° C.                                             Form: Free                                                                    Example 533                                                                   Structure                                                                      -                                                                          4  STR1170##                                                                     - R.sup.2 : 3-CH.sub.3                                                        -                                                                          5  STR1171##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 209-210° C.                                             Form: Free                                                                    Example 534                                                                   Structure                                                                      -                                                                          6  STR1172##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          7  STR1173##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting point: 148-149° C.                                             Form: Free                                                                    Example 535                                                                   Structure                                                                      -                                                                          8  STR1174##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1175##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting point: 202-203° C.                                             Form: Free                                                                    Example 536                                                                   Structure                                                                      -                                                                          0  STR1176##                                                                     - R.sup.2 : 3-CH.sub.3                                                        -                                                                          1  STR1177##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 218-219° C.                                             Form: Free                                                                    Example 537                                                                   Structure                                                                      -                                                                          2  STR1178##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          3  STR1179##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 159-160° C.                                             Form: Free                                                                    Example 538                                                                   Structure                                                                      -                                                                          4  STR1180##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1181##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 201-202° C.                                             Form: Free                                                                    Example 539                                                                   Structure                                                                      -                                                                          6  STR1182##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          7  STR1183##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 205-207° C.                                             Form: Free                                                                    Example 540                                                                   Structure                                                                      -                                                                          8  STR1184##                                                                     - R.sup.2 : 3-OH                                                              -                                                                          9  STR1185##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting point: 201.5-202.5° C.                                         Form: Free                                                                    Example 541                                                                   Structure                                                                      -                                                                          0  STR1186##                                                                     - R.sup.2 : 2-OCH.sub.3                                                       -                                                                          1  STR1187##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 226-228° C.                                             Form: Free                                                                    Example 542                                                                   Structure                                                                      -                                                                          2  STR1188##                                                                     - R.sup.2 : 2-OCH.sub.3                                                       -                                                                          3  STR1189##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 218-221° C.                                             Form: Free                                                                    Example 543                                                                   Structure                                                                      -                                                                          4  STR1190##                                                                     - R.sup.2 : 2-OCH.sub.3                                                       -                                                                          5  STR1191##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 156-157° C.                                             Form: Free                                                                    Example 544                                                                   Structure                                                                      -                                                                          6  STR1192##                                                                     - R.sup.2 : 2-OCH.sub.3                                                       -                                                                          7  STR1193##                                                                     - Crystalline form: White powder                                             NMR analysis: 80)                                                             Form: Free                                                                    Example 545                                                                   Structure                                                                      -                                                                          8  STR1194##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          9  STR1195##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 81)                                                             Form: Free                                                                    Example 546                                                                   Structure                                                                      -                                                                          0  STR1196##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1197##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 82)                                                             Form: Free                                                                    Example 547                                                                   Structure                                                                      -                                                                          2  STR1198##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1199##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 83)                                                             Form: Free                                                                    Example 548                                                                   Structure                                                                      -                                                                          4  STR1200##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1201##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 84)                                                             Form: Free                                                                    Example 549                                                                   Structure                                                                      -                                                                          6  STR1202##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1203##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 85)                                                             Form: Free                                                                    Example 550                                                                   Structure                                                                      -                                                                          8  STR1204##                                                                     - R.sup.2 : 3-OCH.sub.2 CH.sub.3                                              -                                                                          9  STR1205##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 135-136° C.                                             Form: Free                                                                    Example 551                                                                   Structure                                                                      -                                                                          0  STR1206##                                                                     - R.sup.2 : 3-OCH.sub.2 CH.sub.3                                              -                                                                          1  STR1207##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 122-123° C.                                             Form: Free                                                                    Example 552                                                                   Structure                                                                      -                                                                          2  STR1208##                                                                     - R.sup.2 : 3-OCH.sub.2 CH.sub.3                                              -                                                                          3  STR1209##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 118-119° C.                                             Form: Free                                                                    Example 553                                                                   Structure                                                                      -                                                                          4  STR1210##                                                                     -                                                                          5  STR1211##                                                                     -                                                                          6  STR1212##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 145-147° C.                                             Form: Free                                                                    Example 554                                                                   Structure                                                                      -                                                                          7  STR1213##                                                                     -                                                                          8  STR1214##                                                                     -                                                                          9  STR1215##                                                                     - Crystalline form: Light yellow needles                                     Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 169.5-170.5° C.                                         Form: Free                                                                    Example 555                                                                   Structure                                                                      -                                                                          0  STR1216##                                                                     - R.sup.2 : 3-OH                                                              -                                                                          1  STR1217##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 194-195° C.                                             Form: Free                                                                    Example 556                                                                   Structure                                                                      -                                                                          2  STR1218##                                                                     - R.sup.2 : 3-OH                                                              -                                                                          3  STR1219##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: n-Hexane/ethyl acetate                             Melting Point: 202-204° C.                                             Form: Free                                                                    Example 557                                                                   Structure                                                                      -                                                                          4  STR1220##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1221##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 242-243° C.                                             Form: Free                                                                    Example 558                                                                   Structure                                                                      -                                                                          6  STR1222##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1223##                                                                     - Crystalline form: Light yellow powder                                      NMR analysis: 86)                                                             Form: Free                                                                    Example 559                                                                   Structure                                                                      -                                                                          8  STR1224##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1225##                                                                     - Crystalline form: Light yellow powder                                      NMR analysis: 87)                                                             Form: Free                                                                    Example 560                                                                   Structure                                                                      -                                                                          0  STR1226##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1227##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 237-238° C.                                             Form: Free                                                                    Example 561                                                                   Structure                                                                      -                                                                          2  STR1228##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1229##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Dioxane                                            Melting Point: 258-259° C.                                             Form: Free                                                                    Example 562                                                                   Structure                                                                      -                                                                          4  STR1230##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1231##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 182.5-183.5° C.                                         Form: Free                                                                    Example 563                                                                   Structure                                                                      -                                                                          6  STR1232##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1233##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 209-211° C.                                             Form: Free                                                                    Example 564                                                                   Structure                                                                      -                                                                          8  STR1234##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1235##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Dioxane                                            Melting Point: 210-211° C.                                             Form: Free                                                                    Example 565                                                                   Structure                                                                      -                                                                          0  STR1236##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1237##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 176-178° C.                                             Form: Free                                                                    Example 566                                                                   Structure                                                                      -                                                                          2  STR1238##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1239##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 88)                                                             Form: Free                                                                    Example 567                                                                   Structure                                                                      -                                                                          4  STR1240##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1241##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dioxane/water                                      Melting Point: 272-273° C.                                             Form: Free                                                                    Example 568                                                                   Structure                                                                      -                                                                          6  STR1242##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1243##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Dioxane                                            Melting Point: 253-254° C.                                             Form: Free                                                                    Example 569                                                                   Structure                                                                      -                                                                          8  STR1244##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1245##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 248.5-249.5° C.                                         Form: Free                                                                    Example 570                                                                   Structure                                                                      -                                                                          0  STR1246##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1247##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 266.5-267.5° C.                                         Form: Free                                                                    Example 571                                                                   Structure                                                                      -                                                                          2  STR1248##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1249##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 252-253° C.                                             Form: Free                                                                    Example 572                                                                   Structure                                                                      -                                                                          4  STR1250##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1251##                                                                     - Crystalline form: Light yellow powder                                      NMR analysis: 89)                                                             Form: Free                                                                    Example 573                                                                   Structure                                                                      -                                                                          6  STR1252##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1253##                                                                     - Crystalline form: Light brown powder                                       NMR analysis: 90)                                                             Form: Free                                                                    Example 574                                                                   Structure                                                                      -                                                                          8  STR1254##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1255##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether                                      Melting Point: 198.5-199.5° C.                                         Form: Free                                                                    Example 575                                                                   Structure                                                                      -                                                                          0  STR1256##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1257##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 297-299° C.                                             Form: Free                                                                    Example 576                                                                   Structure                                                                      -                                                                          2  STR1258##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          3  STR1259##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 91)                                                             Form: Free                                                                    Example 577                                                                   Structure                                                                      -                                                                          4  STR1260##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1261##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/petroleum ether                            Melting Point: 202-203° C.                                             Form: Free                                                                    Example 578                                                                   Structure                                                                      -                                                                          6  STR1262##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1263##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 92)                                                             Form: Free                                                                    Example 579                                                                   Structure                                                                      -                                                                          8  STR1264##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1265##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 232-233° C.                                             Form: Free                                                                    Example 580                                                                   Structure                                                                      -                                                                          0  STR1266##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1267##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 93)                                                             Form: Free                                                                    Example 581                                                                   Structure                                                                      -                                                                          2  STR1268##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1269##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting point: 256.5-257° C.                                           Form: Free                                                                    Example 582                                                                   Structure                                                                      -                                                                          4  STR1270##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1271##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 193-194° C.                                             Form: Free                                                                    Example 583                                                                   Structure                                                                      -                                                                          6  STR1272##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1273##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 227-230° C.                                             Form: Free                                                                    Example 584                                                                   Structure                                                                      -                                                                          8  STR1274##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1275##                                                                     - Crystalline form: White powder                                             Recrystallization soivent: Ethyl acetate/n-hexane                             Melting Point: 199.5-202° C.                                           Form: Free                                                                    Example 585                                                                   Structure                                                                      -                                                                          0  STR1276##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1277##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 219-220° C.                                             Form: Free                                                                    Example 586                                                                   Structure                                                                      -                                                                          2  STR1278##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1279##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 190-191.5° C.                                           Form: Free                                                                    Example 587                                                                   Structure                                                                      -                                                                          4  STR1280##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1281##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 184-185° C.                                             Form: Free                                                                    Example 588                                                                   Structure                                                                      -                                                                          6  STR1282##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1283##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 223-224° C.                                             Form: Free                                                                    Example 589                                                                   Structure                                                                      -                                                                          8  STR1284##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1285##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 178-181° C.                                             Form: Free                                                                    Example 590                                                                   Structure                                                                      -                                                                          0  STR1286##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1287##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 168-168.5° C.                                           Form: Free                                                                    Example 591                                                                   Structure                                                                      -                                                                          2  STR1288##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1289##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 94)                                                             Form: Free                                                                    Example 592                                                                   Structure                                                                      -                                                                          4  STR1290##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1291##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 95)                                                             Form: Free                                                                    Example 593                                                                   Structure                                                                      -                                                                          6  STR1292##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1293##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 195-197° C.                                             Form: Free                                                                    Example 594                                                                   Structure                                                                      -                                                                          8  STR1294##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1295##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 96)                                                             Form: Free                                                                    Example 595                                                                   Structure                                                                      -                                                                          0  STR1296##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1297##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      Melting Point: 188-189° C.                                             Form: Free                                                                    Example 596                                                                   Structure                                                                      -                                                                          2  STR1298##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1299##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 97)                                                             Form: Free                                                                    Example 597                                                                   Structure                                                                      -                                                                          4  STR1300##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1301##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 98)                                                             Form: Free                                                                    Example 598                                                                   Structure                                                                      -                                                                          6  STR1302##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1303##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 203-204° C.                                             Form: Free                                                                    Example 599                                                                   Structure                                                                      -                                                                          8  STR1304##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1305##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 196-197° C.                                             Form: Free                                                                    Example 600                                                                   Structure                                                                      -                                                                          0  STR1306##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1307##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 99)                                                             Form: Free                                                                    Example 601                                                                   Structure                                                                      -                                                                          2  STR1308##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1309##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 100)                                                            Form: Free                                                                    Example 602                                                                   Structure                                                                      -                                                                          4  STR1310##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1311##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 101)                                                            Form: Free                                                                    Example 603                                                                   Structure                                                                      -                                                                          6  STR1312##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1313##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 102)                                                            Form: Free                                                                    Example 604                                                                   Structure                                                                      -                                                                          8  STR1314##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1315##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 103)                                                            Form: Free                                                                    Example 605                                                                   Structure                                                                      -                                                                          0  STR1316##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1317##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 104)                                                            Form: Free                                                                    Example 606                                                                   Structure                                                                      -                                                                          2  STR1318##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1319##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 105)                                                            Form: Free                                                                    Example 607                                                                   Structure                                                                      -                                                                          4  STR1320##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1321##                                                                     - Crystalline form: Cololess needles                                         Recrystallization solvent: Ethanol                                            Melting Point: 169-171° C.                                             Form: Free                                                                    Example 608                                                                   Structure                                                                      -                                                                          6  STR1322##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1323##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 178-181° C.                                             Form: Free                                                                    Example 609                                                                   Structure                                                                      -                                                                          8  STR1324##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1325##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 187-188° C.                                             Form: Free                                                                    Example 610                                                                   Structure                                                                      -                                                                          0  STR1326##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1327##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 181-183° C.                                             Form: Free                                                                    Example 611                                                                   Structure                                                                      -                                                                          2  STR1328##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1329##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 124-127° C.                                             Form: Free                                                                    Example 612                                                                   Structure                                                                      -                                                                          4  STR1330##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1331##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 179-181° C.                                             Form: Free                                                                    Example 613                                                                   Structure                                                                      -                                                                          6  STR1332##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1333##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 148-150° C.                                             Form: Free                                                                    Example 614                                                                   Structure                                                                      -                                                                          8  STR1334##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1335##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 106)                                                            Form: Free                                                                    Example 615                                                                   Structure                                                                      -                                                                          0  STR1336##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          1  STR1337##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 219-220° C.                                             Form: Free                                                                    Example 616                                                                   Structure                                                                      -                                                                          2  STR1338##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1339##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 226-228° C.                                             Form: Free                                                                    Example 617                                                                   Structure                                                                      -                                                                          4  STR1340##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          5  STR1341##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 107)                                                            Form: Free                                                                    Example 618                                                                   Structure                                                                      -                                                                          6  STR1342##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          7  STR1343##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 108)                                                            Form: Free                                                                    Example 619                                                                   Structure                                                                      -                                                                          8  STR1344##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          9  STR1345##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 109)                                                            Form: Free                                                                    Example 620                                                                   Structure                                                                      -                                                                          0  STR1346##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1347##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 110)                                                            Form: Free                                                                    Example 621                                                                   Structure                                                                      -                                                                          2  STR1348##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1349##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 111)                                                            Form: Free                                                                    Example 622                                                                   Structure                                                                      -                                                                          4  STR1350##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1351##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 112)                                                            Form: Free                                                                    Example 623                                                                   Structure                                                                      -                                                                          6  STR1352##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          7  STR1353##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 113)                                                            Form: Free                                                                    Example 624                                                                   Structure                                                                      -                                                                          8  STR1354##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          9  STR1355##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 114)                                                            Form: Free                                                                    Example 625                                                                   Structure                                                                      -                                                                          0  STR1356##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          1  STR1357##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 115)                                                            Form: Free                                                                    Example 626                                                                   Structure                                                                      -                                                                          2  STR1358##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1359##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 183-184° C.                                             Form: Free                                                                    Example 627                                                                   Structure                                                                      -                                                                          4  STR1360##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1361##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 219-220° C.                                             Form: Free                                                                    Example 628                                                                   Structure                                                                      -                                                                          6  STR1362##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1363##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 240-241° C.                                             Form: Free                                                                    Example 629                                                                   Structure                                                                      -                                                                          8  STR1364##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1365##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 205-206° C.                                             Form: Free                                                                    Example 630                                                                   Structure                                                                      -                                                                          0  STR1366##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1367##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 238-239° C.                                             Form: Free                                                                    Example 631                                                                   Structure                                                                      -                                                                          2  STR1368##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1369##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 233-234° C.                                             Form: Free                                                                    Example 632                                                                   Structure                                                                      -                                                                          4  STR1370##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1371##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 116)                                                            Form: Free                                                                    Example 633                                                                   Structure                                                                      -                                                                          6  STR1372##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          7  STR1373##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 259.5-260.5° C.                                         Form: Free                                                                  ______________________________________                                               80)      .sup.1 H-NMR(CDCl.sub.3) δ; 1.24-5.26 (18H, m),                         6.39-7.59                                                        (13H, m)                                                                      81) .sup.1 H-NMR(CDCl.sub.3) δ; 1.70-2.10 (m, 2H), 2.15-2.60 (m,        12H), 3.56 (t, J=5.8 Hz, 1H), 3.65-3.95 (m, 4H)                               4.05-4.25 (m, 1H), 6.64 (d, J=7.7 Hz, 1H), 6.85-                              7.50 (m, 9H), 8.11 (brs, 1H), 8.42 (d, J=8.8 Hz, 1H)                          82) .sup.1 H-NMR(CDCl.sub.3) δ; 2.00-2.90 (m, 3H), 2.49 (s, 3H),        3.70-3.90 (m, 1H), 4.00-4.20 (m, 1H), 4.80-5.00 (m,                           1H), 6.89 (d, J=6.3 Hz, 1H), 6.95-7.65 (m, 11H),                              7.70 (brs, 1H)                                                                83) .sup.1 H-NMR(CDCl.sub.3) δ; 1.95-2.90 (m, 2H), 2.48 (s, 3H),        2.55 (s, 3H), 3.77 (t, J=5.1 Hz, 1H), 3.92 (t,                                J=6.7 Hz, 2H), 6.72 (d, J=8.0 Hz, 1H), 6.90-7.15                              (m, 2H), 7.15-7.70 (m, 9H), 7.81 (brs, 1H)                                    84) .sup.1 H-NMR(CDCl.sub.3) δ; 2.11 (s, 3H), 2.20-2.40 (m, 2H),        2.50 (s, 3H), 3.80-4.10 (m, 1H), 4.12-4.25 (m, 1H),                           6.03 (t, J=4.3 Hz, 1H), 6.80-7.65 (m, 12H), 7.80                              (brs, 1H)                                                                     85) .sup.1 H-NMR(CDCl.sub.3) δ; 1.80-2.40 (m, 5H), 2.45 (s, 3H),        2.81 (s, 3H), 3.55-3.82 (m, 1H), 4.15-4.40 (m, 1H),                           5.90-6.10 (m, 1H), 6.80-7.80 (m, 12H), 8.67 (brs, 1H)                         86) .sup.1 H-NMR(CDCl.sub.3) δ; 1.95-2.35 (2H, m), 2.75-3.0 (2H,        m), 3.0-5.4 (2H, m), 6.55-7.95 (11H, m), 8.09 (1H, s)                         87) .sup.1 H-NMR(DMSO-d.sub.6) δ; 1.85-2.2 (2H, m), 2.7-2.95                         (2H,                                                             m), 3.5-5.0 (2H, m), 6.8-7.8 (12H, m), 10.60 (1H, s)                          88) .sup.1 H-NMR(CDCl.sub.3) δ; 0.8-1.1 (3H, m), 1.2-2.35 (6H,                         m), 2.35-5.25 (6H, m), 6.63 (1H, d, J=7.7 Hz), 6.8-                           7.6 (9H, m), 7.67 (1H, d, J=8.2 Hz), 7.9-8.15 (1H, m)                         89) .sup.1 H-NMR(CDCl.sub.3) δ; 1.7-2.9 (7H, m),                      4.5-6.5 (3H, m),                                                 6.55-6.75 (1H, m), 6.85-7.6 (12H, m)                                          90) .sup.1 H-NMR(CDCl.sub.3) δ; 1.65-3.1 (7H, m), 4.7-6.6 (3H,                         m), 6.6-6.8 (1H, m), 6.85-7.65 (12H, m)                        91) .sup.1 H-NMR(CDCl.sub.3) δ; 1.8-2.4 (2H, m), 2.86 (2H, t,                        J=6                                                              Hz), 3.1-5.15 (2H, m), 6.85-7.5 (8H, m), 7.5-7.85                             (3H, m), 8.19 (1H, s)                                                         92) .sup.1 H-NMR(CDCl.sub.3) δ; 1.46-2.28 (4H, m), 2.37 (3H, s),        2.58-2.90 (1H, m), 4.57-5.10 (2H, m), 6.59 (1H, d,                            J=7.6 Hz,), 6.91-7.52 (11H, m), 7.62 (1H, d, J=7.6                            Hz), 8.10-8.40 (1H, m)                                                        93) .sup.1 H-NMR(CDCl.sub.3) δ; 1.45-1.91 (2H, m), 1.91-2.65                         (2H,                                                             m), 2.65-2.90 (1H, m), 4.63-5.22 (2H, m), 6.63 (1H,                           d, J=7.4 Hz), 7.34-8.03 (11H, m), 10.16-10.44 (1H, m)                        94) .sup.1 H-NMR(CDCl.sub.3) δ; 1.08-1.47 (3H, m), 1.50-1.97 (2H,        m), 1.97-2.48 (2H, m), 2.65-3.02 (1H, m), 4.00-4.43                           (4H, m), 4.52-5.15 (2H, m), 6.50-6.79 (1H, m),                                6.90-7.70 (10H, m), 8.26-8.60 (1H, m)                                         95) .sup.1 H-NMR(CDCl.sub.3) δ; 1.56-2.67 (4H, m), 2.46 (3H, s),        2.67-3.03 (1H, m), 3.82-4.32 (2H, m), 4.45-5.15                               (2H, m), 5.43-5.83 (1H, m), 6.20-6.45 (1H, m),                                6.50-6.86 (2H, m), 6.86-7.70 (10H, m), 7.76-8.10                              (1H, m)                                                                       96) .sup.1 H-NMR(CDCl.sub.3) δ; 1.52-1.90 (2H, m), 1.90-2.54                         (2H,                                                             m), 2.67-3.05 (1H, m), 3.74-4.32 (2H, m), 4.38-5.17                           (2H, m), 5.52-5.98 (1H, brs), 6.20-6.48 (1H, brs),                            6.55-6.84 (1H, m), 6.89-7.55 (9H, m), 7.55-7.77                               (1H, m), 8.15-8.86 (1H, brs)                                                  97) .sup.1 H-NMR(DMSO-d.sub.6) δ; 1.26-2.49 (4H, m), 2.57-2.93                         (1H, m), 4.07-4.43 (2H, m), 4.44-4.98 (2H, m),                 6.62-6.87 (1H, m), 6.92-7.80 (11H, m), 10.57 (1H,                             s), 12.74 (1H, s)                                                             98) .sup.1 H-NMR(CDCl.sub.3) δ; 1.52-1.89 (2H, m), 1.89-2.56                         (2H,                                                             m), 2.65-3.02 (1H, m), 3.90-4.40 (2H, m), 4.40-5.07                           (2H, m), 6.58-6.78 (1H, m), 6.90-7.70 (10H, m),                               8.57-8.81 (1H, brs)                                                           99) .sup.1 H-NMR(CDCl.sub.3) δ; 1.49-1.89 (2H, m), 1.89-2.60                         (2H,                                                             m), 2.63-3.23 (7H, m), 4.04-4.49 (2H, m), 4.52-5.21                           (2H, m), 6.52-6.80 (1H, m), 6.89-7.84 (10H, m),                               8.08-8.52 (1H, m)                                                            100) .sup.1 H-NMR(CDCl.sub.3) δ; 1.41-1.86 (6H, m), 1.86-2.53                         (4H,                                                             m), 2.25 (3H, s), 2.29 (3H, s), 2.43 (3H, s), 2.60-                           2.97 (1H, m), 3.36-3.77 (2H, m), 4.40-5.10 (2H, m),                           6.54-6.72 (1H, m), 6.88-7.67 (11H, m), 8.27-8.58                              (1H, m)                                                                      101) .sup.1 H-NMR(CDCl.sub.3) δ; 1.44-1.85 (6H, m), 1.85-2.61                         (4H,                                                             m), 2.32 (3H, s), 2.35 (3H, s), 2.61-3.00 (1H, m),                            3.33-3.76 (2H, m), 4.40-5.20 (2H, m), 6.57-6.75                               (1H, m), 6.90-7.70 (11H, m), 8.50-8.93 (1H, m)                               102) .sup.1 H-NMR(CDCl.sub.3) δ; 1.49-2.04 (6H, m), 2.10-3.02                         (5H,                                                             m), 2.47 (6H, s), 3.40-3.88 (2H, m), 4.30-5.17 (2H,                           m), 6.59-6.78 (1H, m), 6.93-7.76 (10H, m), 8.75-                              9.40 (1H, m)                                                                 103) .sup.1 H-NMR(CDCl.sub.3) δ; 1.47-2.47 (6H, m), 2.44 (3H, s),        2.62-3.03 (1H, m), 3.47-4.03 (4H, m), 4.48-5.17                               (2H, m), 6.51-6.74 (1H, m), 6.87-7.62 (11H, m),                               7.62-7.77 (2H, m), 7.77-8.03 (3H, m)                                         104) .sup.1 H-NMR(CDCl.sub.3) δ; 1.42-2.32 (6H, m), 2.44 (3H, s),        2.57-2.97 (1H, m), 3.12-3.83 (4H, m), 4.39-5.13                               (2H, m), 6.50-6.71 (1H, m), 6.90-7.73 (12H, m)                               105) .sup.1 H-NMR(CDCl.sub.3) δ; 1.50-2.63 (9H, m), 2.47 (3H, s),        2.66-3.07 (1H, m), 3.10-3.88 (4H, m), 4.40-5.17                               (2H, m), 5.87-6.23 (1H, brs), 6.60-6.79 (1H, m),                              6.94-7.60 (11H, m), 7.67 (1H, s)                                             106) .sup.1 H-NMR(CDCl.sub.3) δ; 1.20-2.53 (13H, m), 2.63-2.82,                         3.00-3.13, 3.50-3.67, 4.05-4.23 (total 3H, m), 6.55-                          8.00 (13H, m)                                                 107) .sup.1 H-NMR(CDCl.sub.3) δ; 1.41 (9H, s), 1.20-2.55 (10H,                        m),                                                              3.42-4.20 (5.8H, m), 5.00-5.20 (0.2H, m), 6.60-7.67                           (10H, m), 7.99 (1H, brs), 8.26 (1H, d, J=8.4 Hz)                             108) .sup.1 H-NMR(CDCl.sub.3) δ; 1.2-3.0 (10H, m), 3.0-5.2 (6H,                         m), 6.5-7.7 (8H, m), 8.22 (1H, d, J=8.4 Hz), 8.36                             (1H, s)                                                       109) .sup.1 H-NMR(CDCl.sub.3) δ; 1.2-3.0 (10H, m), 3.0-5.2 (6H,                       m),                                                              6.3-7.7 (10H, m)                                                             110) .sup.1 H-NMR(CDCl.sub.3) δ; 1.5-1.7 (1H, m), 2.2-2.7 (2H,                        m),                                                              2.4 (6H, s), 2.7-3.0 (3H, m), 5.1-5.3 (1H, m),                                6.67 (1H, d, J=7.7 Hz), 6.9-7.5 (10H, m), 7.69 (1H,                           d, J=6 Hz), 8.06 (1H, s)                                                     111) .sup.1 H-NMR(CDCl.sub.3) δ; 1.4-1.7 (1H, m), 2.1-2.7 (2H,                        m),                                                              2.40 (6H, s), 2.44 (3H, s), 2.7-3.0 (3H, m), 5.1-                             5.2 (1H, m), 6.68 (1H, d, J=7.8 Hz), 6.9-7.5 (11H,                            m), 7.66 (1H, s)                                                             112) .sup.1 H-NMR(CDCl.sub.3) δ; 1.5-1.8 (1H, m), 2.1-2.7 (2H,                        m),                                                              2.38 (6H, s), 2.7-3.0 (3H, m), 5.1-5.3 (1H, m),                               6.66 (1H, d, J=7.7 Hz), 6.9-7.0 (9H, m), 7.57 (1H,                            d, J=8.3 Hz), 8.42 (1H, s)                                                   113) .sup.1 H-NMR(CDCl.sub.3) δ; 1.5-1.8 (1H, m), 2.1-2.7 (2H,                        m),                                                              2.41 (6H, s), 2.48 (3H, s), 2.7-3.0 (3H, m), 3.68                             (3H, s), 5.2-5.4 (1H, m), 6.6-6.8 (2H, m), 6.9-7.5                            (8H, m), 8.09 (1H, s), 8.26 (1H, d, J=8.1 Hz)                                114) .sup.1 H-NMR(CDCl.sub.3) δ; 1.5-1.7 (1H, m), 2.1-2.3 (1H,                        m),                                                              2.41 (6H, s), 2.4-2.6 (1H, m), 2.8-3.0 (3H, m),                               3.71 (3H, s), 5.2-5.4 (1H, m), 6.6-6.8 (2H, m),                               6.9-7.5 (7H, m), 7.7-7.8 (1H, m), 8.27 (1H, d,                                J=8.4 Hz), 8.57 (1H, s)                                                      115) .sup.1 H-NMR(CDCl.sub.3) δ; 1.5-1.7 (1H, m), 2.1-2.7 (2H,                        m),                                                              2.41 (6H, s), 2.7-3.0 (3H, m), 3.71 (3H, s), 5.2-                             5.4 (1H, m), 6.6-7.6 (8H, m), 7.70 (1H, d, J=8.3                              Hz), 8.24 (1H, d, J=8.5 Hz), 8.59 (1H, s)                                    116) .sup.1 H-NMR(CDCl.sub.3) δ; 1.8-2.3 (3H, m), 2.7-2.9 (2H,                        m),                                                              3.5-3.7 (1H, m), 6.8-8.0 (10H, m), 8.7-9.1 (1H, br)                        ______________________________________                                    

EXAMPLE 634

To a mixture of5-oxo-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(4 g) and pyridine (50 ml) is added hydroxylamine hydrochloride (1.84 g)and the mixture is refluxed for 2.5 hours. The reaction solution isconcentrated and water is added to the resulting residue. Theprecipitated crystal is collected by filtration, and recrystallized fromdioxane/water to give5-hydroxyimino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2 g) as white powder, m.p. 272-273° C.

EXAMPLE 635

5-Chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.8 g) is dissolved in dimethylformamide and thereto is added sodiumazide (0.18 g) at room temperature. The mixture is stirred at roomtemperature overnight, and further reacted with heating at 50° C. for 5hours. Water is added to the reaction mixture and the precipitatedcrystal is collected by filtration to give5-azido-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.68 9) as light brown powder.

¹ H-NMR(CDCl₃) δ; 1.65-3.1 (8H, m), 4.7-6.6 (3H, m), 6.6-6.8 (1H, m),6.85-7.65 (12H, m)

EXAMPLE 636

5-Azido-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.63 g) is dissolved in ethanol and thereto is added 10% Pd-C (0.1 g).The mixture is subjected to catalytic hydrogenation at room temperatureunder 1 atm. of hydrogen. Pd-C is removed by filtration and the filtrateis evaporated. The resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=50:1), andrecrystallized from diethyl ether to give5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.34 g) as white powder, m.p. 198.5-199.5° C.

EXAMPLE 637

To5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.58 g) are added acetic anhydride (8.0 ml) and pyridine (2.0 ml). Themixture is stirred at room temperature for 1 hour. Water is added to thereaction mixture and the precipitated crystal is collected byfiltration, and recrystallized from ethyl acetate/n-hexane to give5-acetyloxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.56 g) as white powder, m.p. 193-194° C.

EXAMPLE 638

5-Ethoxycarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.00 g) is dissolved in methanol (35 ml) and thereto are added aqueousammonia (20 ml) and ammonium chloride (0.50 g). The mixture is heated at100° C. for 3.5 hours in a sealed tube. After cooling, the reactionsolution is concentrated under reduced pressure and acidified withhydrochloric acid, and extracted with dichloromethane. The extract isdried over magnesium sulfate and the solvent is distilled off. Theresulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=15:1) to give5-carbamoylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.68 g) as colorless amorphous.

¹ H-NMR(CDCl₃) δ; 1.56-2.67 (4H, m), 2.46 (3H, s), 2.67-3.03 (1H, m),3.82-4.32 (2H, m), 4.45-5.15 (2H, m), 5.43-5.83 (1H, m), 6.20-6.45 (1H,m), 6.50-6.86 (2H, m), 6.86-7.70 (10H, m), 7.76-8.10 (1H, m)

Using the suitable starting materials, the compounds of the aboveExamples 593 and 594 are obtained in the same manner as in Example 638.

EXAMPLE 639

5-Ethoxycarbonylmethoxy-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.94 g) is dissolved in ethanol (100 ml) and thereto is added 5Naqueous sodium hydroxide solution (0.50 ml). The mixture is stirred atroom temperature for 2 hours. The reaction solution is concentratedunder reduced pressure and to the resulting residue is added dilutedhydrochloric acid and then extracted with dichloromethane. The extractis dried over magnesium sulfate and the solvent is distilled off. Theresulting residue is washed with n-hexane and collected by filtration togive5-carboxymethoxy-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.79 g) as colorless amorphous.

¹ H-NMR(CDCl₃) δ; 1.52-1.89 (2H, m), 1.89-2.56 (2H, m), 2.65-3.02 (1H,m), 3.90-4.40 (2H, m), 4.40-5.07 (2H, m), 6.58-6.78 (1H, m), 6.90-7.70(10H, m), 8.57-8.81 (1H, brs)

Using the suitable starting materials, the compounds of the aboveExamples 595 and 596 are obtained in the same manner as in Example 639.

EXAMPLE 640

5-Carboxymethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.55 g) is dissolved in dimethylformamide (20 ml) and thereto are addeddimethylamine hydrochloride (0.20 g) and diethyl chlorophosphate (0.33g). To the mixture is added triethylamine (1.0 ml) under ice-cooling,and the mixture is stirred under ice-cooling for 30 minutes, and at roomtemperature for more 2 hours. Water is added to the reaction solutionand the precipitated crystal is collected by filtration andrecrystallized from ethyl acetate/n-hexane to give5-dimethylaminocarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.50 g) as colorless prisms, m.p. 203-204° C.

Using the suitable starting materials, the compounds of the aboveExamples 599 and 600 are obtained in the same manner as in Example 640.

EXAMPLE 641

5-[3-(Phthalimid-1-yl)propoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.26 g) is dissolved in ethanol (100 ml) and thereto is added hydrazinehydrate (1.0 ml). The mixture is refluxed with stirring for 1 hour. Thereaction solution is evaporated under reduced pressure and to theresulting residue is added dichloromethane. The insoluble materials areremoved by filtration. The filtrate is purified by silica gel columnchromatography (eluent; dichloromethane:methanol:aqueousammonia=70:10:1) to give5-(3-aminopropoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g) as colorless amorphous.

¹ H-NMR(CDCl₃) δ; 1.42-2.32 (6H, m), 2.44 (3H, s), 2.57-2.97 (1H, m),3.12-3.83 (4H, m), 4.39-5.13 (2H, m), 6.50-6.71 (1H, m), 6.90-7.73 (12H,m)

EXAMPLE 642

A solution of5-dimethylamino-1-[3-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.50 g) in dichloromethane (30 ml) is added dropwise to a solution of1M boron tribromide in dichloromethane (5.46 ml) at -45° C. Aftercompletion of the dropping, the mixture is stirred for 1 day while thetemperature of the reaction mixture is gradually raised to roomtemperature. To the reaction solution is added water and the mixture isneutralized with sodium hydrogen carbonate, and extracted withdichloromethane. The extract is washed with saturated saline solutionand dried over magnesium sulfate. The solvent is distilled off and theresulting residue is purified by silica gel column chromatography(eluent; chloroform:methanol=500:1), and recrystallized frommethanol/diethyl ether to give5-dimethylamino-1-[3-hydroxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.33 g) as white powder, m.p. 201.5-202.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 10, 32, 343, 356, 535, 555 and 556 are obtained in the samemanner as in Example 642.

EXAMPLE 643

To a solution of4-[4-(2-methylbenzoylamino)benzoyl]-3,4-dihydro-2H-1,4-benzazepine (0.5g) in dichloromethane (10 ml) is added m-chloroperbenzoic acid (0.58 9)under ice-cooling, and the mixture is stirred at room temperature for 6hours. The above reaction solution is poured into an aqueous solution ofsodium carbonate (0.6 g) in water (10 ml) and the mixture is extractedwith dichloromethane. The extract is washed with water, and dried overmagnesium sulfate. The solvent is distilled off under reduced pressureand the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=100:1), andrecrystallized from diethyl ether/dichloromethane to give4-[4-(2-methylbenzoylamino)benzoyl]-3,4-dihydro-2H-1,4-benzothiazine-1,1-dioxide(0.49 g) as white powder, m.p. 219-220° C.

Using the suitable starting materials, the compound of the above Example630 is obtained in the same manner as in Example 643.

EXAMPLE 644

To a suspension of4-[4-(2-methylbenzoylamino)benzoyl]-3,4-dihydro-2H-1,4-benzothiazine(0.5 g) in methanol (15 ml) is added an aqueous solution of sodiummetaperiodate (0.28 g) in water (2.5 ml) and the mixture is stirred atroom temperature for 72 hours. Water is added to the reaction solutionand extracted with dichloromethane. The extract is dried over magnesiumsulfate and the solvent is distilled off under reduced pressure. Theresulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=100:1), and recrystallized fromdichloromethane/diethyl ether to give4-[4-(2-methylbenzoylamino)benzoyl]-3,4-dihydro-2H-1,4-benzothiazin-1-oxide(0.34 g) as white powder, m.p. 240-241° C.

Using the suitable starting materials, the compound of the above Example631 is obtained in the same manner as in Example 644.

EXAMPLE 645

5-Hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(3.57 g) is dissolved in dichloromethane (30 ml) and pyridine (1.1 ml),and thereto is added dropwise methanesulfonyl chloride (0.9 ml) in smallportions at 0° C. Then, the mixture is stirred at room temperature for 3days. The solvent is distilled off and the resulting residue is pouredinto ice-water. The precipitated crystal is collected by filtration,washed with water, and dried to give5-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(3.10 g) as light yellow powder.

¹ H-NMR(CDCl₃) δ; 1.7-2.9 (8H, m), 4.5-6.5 (3H, m), 6.55-6.75 (1H, m),6.85-7.6 (12H, m)

EXAMPLE 646

5-Hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2.69 g) is dissolved in dimethylformamide (30 ml) and thereto are added60% sodium hydride dispersion in mineral oil (0.44 9) and ethylbromoacetate (1.00 ml) under ice-cooling, and the mixture is stirred atroom temperature for 4 hours. The reaction solution is poured into anaqueous ammonium chloride solution under ice-cooling, and extracted withethyl acetate. The extract is dried over magnesium sulfate and thesolvent is distilled off. The resulting residue is purified by silicagel column chromatography (eluent; ethyl acetate:n-hexane=1:2), andrecrystallized from ethyl acetate/n-hexane to give5-ethoxycarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl-2,3,4,5-tetrahydro-1H-benzazepine(2.10 g) as white powder, m.p. 178-181° C.

Using the suitable starting materials, the compounds of the aboveExamples 585-588 and 590-606 are obtained in the same manner as inExample 646.

EXAMPLE 647

Using the suitable starting materials, the compounds of the aboveExamples 546 and 578-581 are obtained in the same manner as in Example384.

EXAMPLE 648

Using the suitable starting materials, the compounds of the aboveExamples 537-545, 547, 549-556, 561-564, 566, 568-571, 577, 601-603 and607-625 are obtained in the same manner as in Example 388.

EXAMPLE 649

Using the suitable starting materials, the compounds of the aboveExamples 549, 568-571, 575 and 606 are obtained in the same manner as inExample 389.

EXAMPLE 650

Using the suitable starting materials, the compounds of the aboveExamples 537-545, 547, 549-556, 561-566, 568-571, 575, 577, 607, 608 and613-625 are obtained in the same manner as in Example 390.

EXAMPLE 651

Using the suitable starting materials, the compounds of the aboveExamples 601-603, 605 and 606 are obtained in the same manner as inExample 397.

EXAMPLE 652

Using the suitable starting materials, the compound of the above Example604 is obtained in the same manner as in Example 398.

EXAMPLE 653

Using the suitable starting materials, the following compound isobtained in the same manner as in Examples 1, 382, 388 and 390.

5-Methylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 184.5-185.5° C. (recrystallized from ethanol)

Using the suitable starting materials, the compounds of the followingTable 4 are obtained in the same manner as in Examples 1 and 382.

                  TABLE 4                                                         ______________________________________                                        1 #STR1374##                                                                  ______________________________________                                        Example 654                                                                     Structure                                                                   2  STR1375##                                                                     - R.sup.2 : 2-OH                                                              -                                                                          3  STR1376##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 193.5-196° C.                                           Form: Free                                                                    Example 655                                                                   Structure                                                                      -                                                                          4  STR1377##                                                                     - R.sup.2 : 2-OH                                                              -                                                                          5  STR1378##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 195-198° C.                                             Form: Free                                                                    Example 656                                                                   Structure                                                                      -                                                                          6  STR1379##                                                                     - R.sup.2 : 2-OC.sub.2 H.sub.5                                                -                                                                          7  STR1380##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 230.5-231.5° C.                                         Form: Free                                                                    Example 657                                                                   Structure                                                                      -                                                                          8  STR1381##                                                                     - R.sup.2 : 2-OC.sub.2 H.sub.5                                                -                                                                          9  STR1382##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 223-224.5° C.                                           Form: Free                                                                    Example 658                                                                   Structure                                                                      -                                                                          0  STR1383##                                                                     - R.sup.2 : 2-OC.sub.2 H.sub.5                                                -                                                                          1  STR1384##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 173-174° C.                                             Form: Free                                                                    Example 659                                                                   Structure                                                                      -                                                                          2  STR1385##                                                                     - R.sup.2 : 3-CH.sub.3                                                        -                                                                          3  STR1386##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 174-175° C.                                             Form: Free                                                                    Example 660                                                                   Structure                                                                      -                                                                          4  STR1387##                                                                     - R.sup.2 : 3-CH.sub.3                                                        -                                                                          5  STR1388##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 198-200° C.                                             Form: Free                                                                    Example 661                                                                   Structure                                                                   6  STR1389##                                                                     - R.sup.2 : 3-CH.sub.3                                                        -                                                                          7  STR1390##                                                                     - Crystalline form: White powder                                             Recrystaliization solvent: Methanol/n-hexane                                  Melting Point: 149-150.5° C.                                           Form: Free                                                                    Example 662                                                                   Structure                                                                      -                                                                          8  STR1391##                                                                     - R.sup.2 : 2-CH.sub.3                                                        -                                                                          9  STR1392##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 183-185° C.                                             Form: Free                                                                    Example 663                                                                   Structure                                                                      -                                                                          0  STR1393##                                                                     - R.sup.2 : 2-CH.sub.3                                                        -                                                                          1  STR1394##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 203-207° C.                                             Form: Free                                                                    Example 664                                                                   Structure                                                                      -                                                                          2  STR1395##                                                                     - R.sup.2 : 2-CH.sub.3                                                        -                                                                          3  STR1396##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 221-222° C.                                             Form: Free                                                                    Example 665                                                                   Structure                                                                      -                                                                          4  STR1397##                                                                     - R.sup.2 : 2-F                                                               -                                                                          5  STR1398##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 189-191° C.                                             Form: Free                                                                    Example 666                                                                   Structure                                                                   6  STR1399##                                                                     - R.sup.2 : 2-F                                                               -                                                                          7  STR1400##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 215.5-217° C.                                           Form: Free                                                                    Example 667                                                                   Structure                                                                      -                                                                          8  STR1401##                                                                     - R.sup.2 : 2-F                                                               -                                                                          9  STR1402##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 192-194° C.                                             Form: Free                                                                    Example 668                                                                   Structure                                                                      -                                                                          0  STR1403##                                                                     - R.sup.2 : 3-F                                                               -                                                                          1  STR1404##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 195-196° C.                                             Form: Free                                                                    Example 669                                                                   Structure                                                                      -                                                                          2  STR1405##                                                                     - R.sup.2 : 3-F                                                               -                                                                          3  STR1406##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 202-204.5° C.                                           Form: Free                                                                    Example 670                                                                   Structure                                                                      -                                                                          4  STR1407##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1408##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 183-187° C.                                             Form: Free                                                                    Example 671                                                                   Structure                                                                      -                                                                          6  STR1409##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1410##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 120-122° C.                                             Form: Free                                                                    Example 672                                                                   Structure                                                                      -                                                                          8  STR1411##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1412##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Chloroform/                                        diethyl ether                                                                 Melting Point: 208-210° C.                                             Form: Free                                                                    Example 673                                                                   Structure                                                                      -                                                                          0  STR1413##                                                                     - R.sup.2 : 2-OCH.sub.3                                                       -                                                                          1  STR1414##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 182-183° C.                                             Form: Free                                                                    Example 674                                                                   Structure                                                                      -                                                                          2  STR1415##                                                                     - R.sup.2 : 2-OCH.sub.3                                                       -                                                                          3  STR1416##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 257-259° C.                                             Form: Free                                                                    Example 675                                                                   Structure                                                                      -                                                                          4  STR1417##                                                                     - R.sup.2 : 2-OC.sub.2 H.sub.5                                                -                                                                          5  STR1418##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/                                   diethyl ether                                                                 Melting Point: 134-135° C.                                             Form: Free                                                                    Example 676                                                                   Structure                                                                      -                                                                          6  STR1419##                                                                     - R.sup.2 : 2-OCH.sub.3                                                       -                                                                          7  STR1420##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 167-169° C                                              Form: Free                                                                    Example 677                                                                   Structure                                                                      -                                                                          8  STR1421##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          9  STR1422##                                                                     - Crystalline form: Light brown prisms                                       Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 170-172° C.                                             Form: Free                                                                    Example 678                                                                   Structure                                                                      -                                                                          0  STR1423##                                                                     -                                                                          1  STR1424##                                                                     -                                                                          2  STR1425##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 181.5-182.5° C.                                         Form: Free                                                                    Example 679                                                                   Structure                                                                      -                                                                          3  STR1426##                                                                     -                                                                          4  STR1427##                                                                     -                                                                          5  STR1428##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 176.5-177° C.                                           Form: Free                                                                    Example 680                                                                   Structure                                                                      -                                                                          6  STR1429##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          7  STR1430##                                                                     - Crystalline form: Yellow amorphous                                         NMR analysis: 117)                                                            Form: Free                                                                    Example 681                                                                   Structure                                                                      -                                                                          8  STR1431##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          9  STR1432##                                                                     - Crystalline form: Yellow amorphous                                         NMR analysis: 118)                                                            Form: Free                                                                    Example 682                                                                   Structure                                                                      -                                                                          0  STR1433##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1434##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 236-239° C.                                             Form: Free                                                                    Example 683                                                                   Structure                                                                      -                                                                          2  STR1435##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1436##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 153-154° C.                                             Form: Free                                                                    Example 684                                                                   Structure                                                                      -                                                                          4  STR1437##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1438##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 128-130° C.                                             Form: Free                                                                    Example 685                                                                   Structure                                                                      -                                                                          6  STR1439##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1440##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 231-234° C.                                             Form: Free                                                                    Example 686                                                                   Structure                                                                      -                                                                          8  STR1441##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1442##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate                                      Melting Point: 246-248° C.                                             Form: Free                                                                    Example 687                                                                   Structure                                                                      -                                                                          0  STR1443##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1444##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      Melting Point: 248-248.5° C.                                           Form: Free                                                                    Example 688                                                                   Structure                                                                      -                                                                          2  STR1445##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1446##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/                                   diethyl ether                                                                 Melting Point: 204-205° C.                                             Form: Free                                                                    Example 689                                                                   Structure                                                                      -                                                                          4  STR1447##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1448##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/                                   diethyl ethyl                                                                 Melting Point: >300° C.                                                NMR analysis: 119)                                                            Form: Free                                                                    Example 690                                                                   Structure                                                                      -                                                                          6  STR1449##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1450##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/                                   diethyl ether                                                                 Melting Point: 292-294° C.                                             Form: Free                                                                    Example 691                                                                   Structure                                                                      -                                                                          8  STR1451##                                                                     - R.sup.2 : 2-N(CH.sub.3).sub.2                                               -                                                                          9  STR1452##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 120)                                                            Form: Free                                                                    Example 692                                                                   Structure                                                                      -                                                                          0  STR1453##                                                                     - R.sup.2 : 2-N(CH.sub.3).sub.2                                               -                                                                          1  STR1454##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 121)                                                            Form: Free                                                                    Example 693                                                                   Structure                                                                      -                                                                          2  STR1455##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          3  STR1456##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 122)                                                            Form: Free                                                                    Example 694                                                                   Structure                                                                      -                                                                          4  STR1457##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1458##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 123)                                                            Form: Free                                                                    Example 695                                                                   Structure                                                                      -                                                                          6  STR1459##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          7  STR1460##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 198.5-199° C.                                           Form: Free                                                                    Example 696                                                                   Structure                                                                      -                                                                          8  STR1461##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          9  STR1462##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 168-170° C.                                             Form: Free                                                                    Example 697                                                                   Structure                                                                      -                                                                          0  STR1463##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          1  STR1464##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 175-176° C.                                             Form: Free                                                                    Example 698                                                                   Structure                                                                      -                                                                          2  STR1465##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          3  STR1466##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 177-178° C.                                             Form: Free                                                                    Example 699                                                                   Structure                                                                      -                                                                          4  STR1467##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1468##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 222-223.5° C.                                           Form: Free                                                                    Example 700                                                                   Structure                                                                      -                                                                          6  STR1469##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          7  STR1470##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 243-244° C.                                             Form: Free                                                                    Example 701                                                                   Structure                                                                      -                                                                          8  STR1471##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1472##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 180-181° C.                                             Form: Free                                                                    Example 702                                                                   Structure                                                                      -                                                                          0  STR1473##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1474##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 124)                                                            Form: Free                                                                    Example 703                                                                   Structure                                                                      -                                                                          2  STR1475##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1476##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 231-233° C.                                             Form: Free                                                                    Example 704                                                                   Structure                                                                      -                                                                          4  STR1477##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1478##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 196-198° C.                                             Form: Free                                                                    Example 705                                                                   Structure                                                                      -                                                                          6  STR1479##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          7  STR1480##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 125)                                                            Form: Free                                                                    Example 706                                                                   Structure                                                                      -                                                                          8  STR1481##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          9  STR1482##                                                                     - Crystalline form: Yellow amorphous                                         NMR analysis: 126)                                                            Form: Free                                                                    Example 707                                                                   Structure                                                                      -                                                                          0  STR1483##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1484##                                                                     - Crystalline form: Yellow powder                                            Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 146-147° C.                                             Form: Free                                                                    Example 708                                                                   Structure                                                                      -                                                                          2  STR1485##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1486##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 127)                                                            Form: Free                                                                    Example 709                                                                   Structure                                                                      -                                                                          4  STR1487##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1488##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 220-221° C.                                             Form: Free                                                                    Example 710                                                                   Structure                                                                      -                                                                          6  STR1489##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1490##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/                                     dichloromethane                                                               Melting Point: 170-172° C.                                             Form: Free                                                                    Example 711                                                                   Structure                                                                      -                                                                          8  STR1491##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1492##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 128)                                                            Form: Free                                                                    Example 712                                                                   Structure                                                                      -                                                                          0  STR1493##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1494##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 224-225° C.                                             Form: Free                                                                    Example 713                                                                   Structure                                                                      -                                                                          2  STR1495##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          3  STR1496##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 193-196° C.                                             Form: Free                                                                    Example 714                                                                   Structure                                                                      -                                                                          4  STR1497##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1498##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 212-214° C.                                             Form: Free                                                                    Example 715                                                                   Structure                                                                      -                                                                          6  STR1499##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          7  STR1500##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 211-213° C.                                             Form: Free                                                                    Example 716                                                                   Structure                                                                      -                                                                          8  STR1501##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          9  STR1502##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 213-215° C.                                             Form: Free                                                                    Example 717                                                                   Structure                                                                      -                                                                          0  STR1503##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          1  STR1504##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 199-201° C.                                             Form: Free                                                                    Example 718                                                                   Structure                                                                      -                                                                          2  STR1505##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          3  STR1506##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethnaol                                            Melting Point: 238-240° C.                                             Form: Free                                                                    Example 719                                                                   Structure                                                                      -                                                                          4  STR1507##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1508##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 188-189° C.                                             Form: Free                                                                    Example 720                                                                   Structure                                                                      -                                                                          6  STR1509##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1510##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Dioxane/water                                      Melting Point: 135.5-137° C.                                           Form: Free                                                                    Example 721                                                                   Structure                                                                      -                                                                          8  STR1511##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1512##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Isopropyl alcohol/                                 petroleum ether                                                               Melting Point: 192-193° C.                                             Form: Free                                                                    Example 722                                                                   Structure                                                                      -                                                                          0  STR1513##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1514##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate                                      Melting Point: 239-240° C.                                             Form: Free                                                                    Example 723                                                                   Structure                                                                      -                                                                          2  STR1515##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1516##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 129)                                                            Form: Free                                                                    Example 724                                                                   Structure                                                                      -                                                                          4  STR1517##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1518##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 130)                                                            Form: Free                                                                    Example 725                                                                   Structure                                                                      -                                                                          6  STR1519##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1520##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/petroleum ether                            Melting Point: 193-194° C.                                             Form: Free                                                                    Example 726                                                                   Structure                                                                      -                                                                          8  STR1521##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1522##                                                                     - Crystalline form: Light yellow prisms                                      Recrystallization solvent: Ethanol                                            Melting Point: 245.5-247° C.                                           Form: Free                                                                    Example 727                                                                   Structure                                                                      -                                                                          0  STR1523##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1524##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol/petroleum ether                            Melting Point: 142-144° C.                                             Form: Free                                                                    Example 728                                                                   Structure                                                                      -                                                                          2  STR1525##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1526##                                                                     - Crystalline form: Light yellow prisms                                      Recrystallization solvent: Ethanol                                            Melting Point: 214-217° C.                                             Form: Free                                                                    Example 729                                                                   Structure                                                                      -                                                                          4  STR1527##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1528##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 205-207° C.                                             Form: Free                                                                    Example 730                                                                   Structure                                                                      -                                                                          6  STR1529##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1530##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 201-203° C.                                             Form: Free                                                                    Example 731                                                                   Structure                                                                      -                                                                          8  STR1531##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1532##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 180-182° C.                                             Form: Free                                                                    Example 732                                                                   Structure                                                                      -                                                                          0  STR1533##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1534##                                                                     - Crystalline form: Light yellow scales                                      Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 178-180° C.                                             Form: Free                                                                    Example 733                                                                   Structure                                                                      -                                                                          2  STR1535##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1536##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 208-213° C.                                             Form: Free                                                                    Example 734                                                                   Structure                                                                      -                                                                          4  STR1537##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1538##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 175-177° C.                                             Form: Free                                                                    Example 735                                                                   Structure                                                                      -                                                                          6  STR1539##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1540##                                                                     - Crystalline form: White powder                                             NMR analysis: 131)                                                            Form: Free                                                                    Example 736                                                                   Structure                                                                      -                                                                          8  STR1541##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1542##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/                                     /n-hexane                                                                     Melting Point: 277-279° C.                                             Form: Free                                                                    Example 737                                                                   Structure                                                                      -                                                                          0  STR1543##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1544##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 132)                                                            Form: Free                                                                    Example 738                                                                   Structure                                                                      -                                                                          2  STR1545##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1546##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 133)                                                            Form: Free                                                                    Example 739                                                                   Structure                                                                      -                                                                          4  STR1547##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1548##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 134)                                                            Form: Free                                                                    Example 740                                                                   Structure                                                                      -                                                                          6  STR1549##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1550##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 135)                                                            Form: Free                                                                    Example 741                                                                   Structure                                                                      -                                                                          8  STR1551##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1552##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 213-214° C.                                             Form: Free                                                                    Example 742                                                                   Structure                                                                      -                                                                          0  STR1553##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1554##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 216-217° C.                                             Form: Free                                                                    Example 743                                                                   Structure                                                                      -                                                                          2  STR1555##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          3  STR1556##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 165-167° C.                                             Form: Free                                                                    Example 744                                                                   Structure                                                                      -                                                                          4  STR1557##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1558##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 202-206° C.                                             Form: Free                                                                    Example 745                                                                   Structure                                                                      -                                                                          6  STR1559##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          7  STR1560##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 220-221.5° C.                                           Form: Free                                                                    Example 746                                                                   Structure                                                                      -                                                                          8  STR1561##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1562##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 186-186.5° C.                                           Form: Free                                                                    Example 747                                                                   Structure                                                                      -                                                                          0  STR1563##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          1  STR1564##                                                                     - Crystalline form: Colorless amorphous                                      NMR anaylsis: 136)                                                            Form: Free                                                                    Example 748                                                                   Structure                                                                      -                                                                          2  STR1565##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1566##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 136-140° C.                                             Form: Free                                                                    Example 749                                                                   Structure                                                                      -                                                                          4  STR1567##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1568##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 151-153° C.                                             Form: Free                                                                    Example 750                                                                   Structure                                                                      -                                                                          6  STR1569##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1570##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 155-156° C.                                             Form: Free                                                                    Example 751                                                                   Structure                                                                      -                                                                          8  STR1571##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1572##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 189-190° C.                                             Form: Free                                                                    Example 752                                                                   Structure                                                                      -                                                                          0  STR1573##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1574##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 188-190° C.                                             Form: Free                                                                    Example 753                                                                   Structure                                                                      -                                                                          2  STR1575##                                                                     - R.sup.2 : H                                                                 -                                                                          3  STR1576##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 233-235° C.                                             Form: Free                                                                    Example 754                                                                   Structure                                                                      -                                                                          4  STR1577##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1578##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 137)                                                            Form: Free                                                                    Example 755                                                                   Structure                                                                      -                                                                          6  STR1579##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1580##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 176-179° C.                                             Form: Free                                                                    Example 756                                                                   Structure                                                                      -                                                                          8  STR1581##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR1582##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 183-185° C.                                             Form: Free                                                                  ______________________________________                                          117)   .sup.1 H-NMR(CDCl.sub.3)δ; 1.3-2.3(4H, m), 3.1-3.4(3H, m),        3.8-4.6(2H, m), 5.0-5.3(2H, m), 5.8-6.1(1H, m),                               6.8-8.5(11H, m)                                                              118) .sup.1 H-NMR(CDCl.sub.3)δ; 1.6-2.2(4H, m), 2.46, 2.53(3H,                   each s), 3.1-3.5(3H, m), 3.8-4.6(2H, m), 5.0-5.3                      (2H, m), 5.8-6.1(1H, m), 6.8-8.8(11H, m)                                     119) .sup.1 H-NMR(DMSO-d.sub.6)δ; 2.33(3H, s), 3.36(2H, m),                      3.89(1H, m), 4.41(1H, m), 5.07(1H, m), 5.40(1H,                       d, J=14.8Hz), 6.85(1H, d, J=7.2Hz), 7.15-7.65                                 (11H, m), 10.35(1H, s)                                                       120) .sup.1 H-NMR(CDCl.sub.3)δ; 1.25-5.05(22H, m), 6.65-7.65                     (11H, m), 7.75-8.25(1H, m)                                           121) .sup.1 H-NMR(CDCl.sub.3)δ; 1.15-5.05(19H, m), 6.75-7.85                     (11H, m), 7.75-8.25(1H, m)                                           122) .sup.1 H-NMR(CDCl.sub.3)δ; 1.25-2.85(8H, m), 2.95-4.95                      (2H, m), 6.75-7.85(10H, m), 9.25-9.75(1H, m)                         123) .sup.1 H-NMR(CDCl.sub.3)δ; 0.20-0.70(4H, m), 0.95-2.35(6H,                  m), 2.65-5.00(2H, m), 6.75-7.90(10H, m), 8.65-                        9.25(1H, m)                                                                  124) .sup.1 H-NMR(CDCl.sub.3)δ; 1.20-3.15(11H, m), 3.45-3.70                     (1H, m), 4.05-5.20(1H, m), 6.60-7.65(10H, m),                         8.15-8.45(2H, m)                                                             125) .sup.1 H-NMR(CDCl.sub.3)δ; 1.19(3H, t, J=7Hz), 1.25-3.25                    (8H, m), 3.46(2H, q, J=7Hz), 3.40-4.10(3H, m),                        4.45-5.10(1H, m), 6.65-7.75(12H, m), 8.30-8.60                                (1H, m)                                                                      126) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10-1.30(3H, m), 1.50-2.35(4H,                  m), 2.65-3.05(2H, m), 3.35-3.60(2H, m), 3.80-4.05                     (2H, m), 4.65-5.15(2H, m), 6.55-7.85(12H, m),                                 8.35-8.65(1H, m)                                                             127) .sup.1 H-NMR(CDCl.sub.3)δ; 1.20(3H, t, J=7Hz), 1.10-3.15                    (11H, m), 3.45-3.65(3H, m), 3.88(2H, s), 3.95-                        5.15(1H, m), 6.55-7.65(13H, m), 8.37(1H, s)                                  128) .sup.1 H-NMR(CDCl.sub.3)δ; 2.45(3H, s), 3.40(3H, s), 4.01                   (2H, m), 4.38(2H, m), 7.20-7.77(13H, m)                              129) .sup.1 H-NMR(CDCl.sub.3)δ; 1.35-4.55(22H, m), 6.3-7.8(13H,                  m)                                                                   130) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10(6H, t, J=7Hz), 1.35-5.1                     (23H, m), 6.55-7.8(13H, m)                                           131) .sup.1 H-NMR(CDCl.sub.3)δ; 1.94-3.21(3H, m), 3.30-4.82(3H,                  m), 6.57(1H, d, J=7.5Hz), 6.86-8.10(11H, m),                          8.72(1H, br)                                                                 132) .sup.1 H-NMR(DMSO-d.sub.6)δ; 1.57-1.85(2H, m), 1.85-2.28                    (2H, m), 2.33(3H, s), 2.64-2.86(1H, m), 4.53-5.07                     (1H, m), 5.79-5.94(1H, m), 6.47-7.68(2H, br),                                 6.64-6.77(1H, m), 6.96-7.62(12H, m)                                          133) .sup.1 H-NMR(CDCl.sub.3)δ; 1.61-1.97(2H, m), 2.00-2.54(2H,                  m), 2.47(3H, s), 2.60-3.23(7H, m), 4.76-5.22(1H,                      m), 5.94-6.19(1H, m), 6.61-6.74(1H, m), 6.91-7.62                             (12H, m)                                                                     134) .sup.1 H-NMR(CDCl.sub.3)δ; 1.68-1.97(2H, m), 2.03-2.53(2H,                  m), 2.61-3.24(7H, m), 4.76-5.22(1H, m), 5.97-6.17                     (1H, m), 6.59-6.74(1H, m), 6.92-7.13(1H, m),                                  7.13-7.58(9H, m), 7.66-7.85(1H, m), 7.85-8.00                                 (1H, m)                                                                      135) .sup.1 H-NMR(CDCl.sub.3)δ; 1.57-1.93(2H, m), 1.93-2.54(2H,                  m), 2.54-2.72(1H, m), 2.79-3.09(3H, m), 3.90-4.32                     (2H, m), 4.49-5.18(2H, m), 6.31-6.93(2H, m),                                  6.96-7.63(10H, m), 7.63-7.89(1H, m), 7.89-8.16                                (1H, m)                                                                      136) .sup.1 H-NMR(CDCl.sub.3)δ; 1.44-1.95(2H, m), 1.95-2.28(2H,                  m), 2.40-2.67(3H, m), 2.73-3.38(3H, m), 3.40-3.97                     (1H, m), 4.50-5.20(1H, m), 6.67-8.11(11H, m)                                 137) .sup.1 H-NMR(CDCl.sub.3)δ; 1.50-2.10(3H, m), 2.10-2.28(1H,                  m), 2.36(3H, s), 2.48(3H, s), 2.68-2.97(1H, m),                       3.26-3.47(1H, m), 4.16(1H, d, J=13.8Hz), 4.25                                 (1H, d, J=13.8Hz), 5.95(1H, brs), 6.60-6.76(1H,                               m), 6.97-7.52(8H, m), 7.52-7.73(2H, m), 7.73-7.97                             (2H, m)                                                                    ______________________________________                                    

EXAMPLE 757

A mixture of5-dimethylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(10 g), methyl iodide (1.7 ml) and chloroform (10 ml) is heated withstirring at 100° C. for 3 hours in an autoclave. After completion of thereaction, the solvent is distilled off under reduced pressure and theresulting residue is dissolved in methanol. The mixture is treated withIRA-400 (trade mark; Organo Co., Ltd., OH⁻ type). Methanol is distilledoff and the resulting residue is suspended in t-butyl alcohol (90 ml),and thereto is added potassium t-butoxide (2.3 g). The mixture isrefluxed for 5 hours. The solvent is distilled off under reducedpressure, and the resulting residue is dissolved in dichloromethane. Themixture is washed successively with water and saturated saline solutionand dried over magnesium sulfate. The solvent is distilled off and tothe resulting residue is added dichloromethane/diethyl ether. Theprecipitated crude crystal is recrystallized from ethanol to give1-[4-(2-chlorobenzoylamino)benzoyl]-2,3-dihydro-1H-benzazepine (5.15 g)as colorless needles, m.p. 205-207° C.

EXAMPLE 758

1-[4-(2-Chlorobenzoylamino)benzoyl]-2,3-dihydro-1H-benzazepine (4.7 g)is dissolved in dichloromethane (50 ml) and thereto is added 80%m-chloroperbenzoic acid (3 g). The mixture is stirred at roomtemperature overnight. The dichloromethane layer is washed successivelywith saturated aqueous sodium hydrogen carbonate solution and saturatedsaline solution, and the solvent is distilled off under reducedpressure. The resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=50:1) to give4,5-epoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(4.26 g) as white powder.

¹ H-NMR(CDCl₃) δ; 1.94-3.21 (3H, m), 3.30-4.82 (3H, m), 6.57 (1H, d,J=7.5 Hz), 6.86-8.10 (11H, m), 8.72 (1H, brs)

EXAMPLE 759

A mixture of4,5-epoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.5 g), dimethylamine hydrochloride (2.6 g), triethylamine (4.5 g) andmethanol (15 ml) is refluxed for 19 hours. After completion of thereaction, the solvent is distilled off and the resulting residue isdissolved in dichloromethane. The mixture is washed successively withwater and saturated saline solution. The solvent is distilled off andthe resulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=50:1), and recrystallized fromethanol/diethyl ether to givetrans-5-dimethylamino-4-hydroxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.38 g) as colorless needles, m.p. 180-182° C.

Using the suitable starting materials, the compounds of the aboveExamples 733 and 734 are obtained in the same manner as in Example 759.

EXAMPLE 760

Methyltriphenylphosphonium bromide (4.30 g) is suspended intetrahydrofuran (100 ml) and thereto is added potassium t-butoxide (1.58g) under ice-cooling. The mixture is stirred at -5° C. for 1 hour andthereto is added5-oxo-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.60 g) and the mixture is stirred at room temperature for 1 hour. Thereaction solution is poured into ice-water (200 ml) and extracted withethyl acetate. The extract is washed with saturated saline solution anddried over magnesium sulfate. The solvent is distilled off and theresulting residue is purified by silica gel column chromatography(eluent; ethyl acetate:n-hexane=1:2), and recrystallized from ethylacetate/n-hexane to give5-methylidene-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.34 g) as white powder, m.p. 216-217° C.

Using the suitable starting materials, the compound of the above Example743 is obtained in the same manner as in Example 760.

EXAMPLE 761

5-Methylidene-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2.84 g) is suspended in tetrahydrofuran (50 ml) and thereto is added 1M solution of boran-tetrahydrofuran complex in tetrahydrofuran (43 ml).The mixture is stirred at room temperature for 6 hours. After completionof the reaction, the reaction solution is cooled with ice, and theretois added water (70 ml). After termination of the evolution of hydrogengas, to the reaction solution are added 25% aqueous sodium hydroxidesolution (7.0 ml), and subsequently 31% aqueous hydrogen peroxidesolution (4.7 ml), and the mixture is heated with stirring at 50° C. for1 hour. After cooling, to the reaction solution is added saturatedsaline solution and the tetrahydrofuran layer is collected, washed withsaturated saline solution and dried over magnesium sulfate. The solventis distilled off and the resulting residue is recrystallized from ethylacetate/n-hexane to give5-hydroxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.96 g) as white powder, m.p. 202-206° C.

Using the suitable starting materials, the compound of the above Example745 is obtained in the same manner as in Example 761.

EXAMPLE 762

5-Methylidene-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.81 g) is dissolved in dichloromethane (30 ml) and thereto is addedm-chloroperbenzoic acid (0.57 g). The mixture is stirred at roomtemperature for 15 hours. After completion of the reaction, the reactionsolution is washed successively with aqueous sodium hydrogensulfitesolution, aqueous sodium hydrogen carbonate solution and saturatedsaline solution, and dried over magnesium sulfate. The solvent isdistilled off and the resulting residue is purified with silica gelcolumn chromatography (eluent; ethyl acetate:n-hexane=2:3) to give5,5-epoxy-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g) as colorless amorphous.

¹ H-NMR(CDCl₃) δ; 1.44-1.95 (2H, m), 1.95-2.28 (2H, m), 2.40-2.67 (3H,m), 2.73-3.38 (3H, m), 3.40-3.97 (1H, m), 4.50-5.20 (1H, m), 6.67-8.11(11H, m)

Using the suitable starting materials, the compound of the above Example746 is obtained in the same manner as in Example 762.

EXAMPLE 763

To5-methylidene-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.60 g) are added successively t-butyl alcohol (6.0 ml), water (1.2ml), pyridine (0.3 ml), osmium tetroxide (1.2 mg) and trimethylamineN-oxide dihydrate (0.22 9), and the mixture is refluxed with stirringfor 2.5 hours. After cooling, to the reaction solution is added 20%aqueous sodium hydrogen-sulfite solution (10 ml), and the mixture isstirred at room temperature for 1.5 hour. The reaction solution isextracted with a mixture of ethyl acetate/tetrahydrofuran (1:1). Theextract is washed successively with diluted hydrochloric acid andsaturated saline solution, and dried over magnesium sulfate. The solventis distilled off and the resulting residue is recrystallized from ethylacetate/n-hexane to give5-hydroxymethyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.55 g) as white powder, m.p. 136-140° C.

Using the suitable starting materials, the compound of the above Example749 is obtained in the same manner as in Example 763.

EXAMPLE 764

To5-hydroxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.40 g) are added acetic anhydride (4.0 ml) and pyridine (0.5 ml), andthe mixture is stirred at room temperature for 5 hours. After completionof the reaction, the reaction solution is poured into ice-water andextracted with ethyl acetate. The extract is washed successively withdiluted hydrochloric acid and saturated saline solution, and dried overmagnesium sulfate. The solvent is distilled off and the resultingresidue is recrystallized from ethyl acetate/n-hexane to give5-acetyloxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.43 g) as colorless needles, m.p. 155-156° C.

EXAMPLE 765

5-Hydroxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g) is dissolved in a mixture (30 ml) ofdichloromethane/acetonitrile (1:1) and thereto are added methanesulfonylchloride (0.8 ml) and pyridine (1.0 ml), and the mixture is refluxedwith stirring for 2 hours. After cooling, the reaction solution isevaporated under reduced pressure and to the resulting residue is addedwater and then extracted with ethyl acetate. The extract is washedsuccessively with diluted hydrochloric acid and saturated salinesolution, and dried over magnesium sulfate. The solvent is distilled offand the resulting residue is recrystallized from ethyl acetate/n-hexaneto give5-methanesulfonyloxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.72 g) as white powder, m.p. 189-190° C.

EXAMPLE 766

5-Methanesulfonyloxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.49 g) is dissolved in a mixture (25 ml) ofacetonitrile/dimethylformamide (4:1) and thereto is added sodium azide(0.11 g). The mixture is refluxed with stirring for 3.5 hours. Aftercooling, the reaction solution is poured into ice-water (40 ml),extracted with ethyl acetate, washed with saturated saline solution, anddried over magnesium sulfate. The solvent is distilled off and theresulting residue is purified by silica gel column chromatography(eluent; ethyl acetate:n-hexane=1:2), and recrystallized from ethylacetate/n-hexane to give5-azidomethyl-1-[4-(2-methylbenzoylamino)benzoly]-2,3,4,5-tetrahydro-1H-benzazepine(0.29 9) as white powder, m.p. 188-189° C.

EXAMPLE 767

5-Azidomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.27 g) is suspended in ethanol (50 ml) and the mixture is subjected tocatalytic hydrogenation at room temperature under 3 kg/cm² for 6 hoursby using 10% Pd-C (27 mg). The catalyst is removed by filtration withcelite and the filtrate is distilled off and the resulting residue isrecrystallized from ethanol to give5-aminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.12 g) as colorless needles, m.p. 233-235° C.

EXAMPLE 768

To5,5-epoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.30 g) is added 30% solution of methylamine in methanol (30 ml), andthe mixture is refluxed for 14 hours. After compeltion of the reaction,the reaction solution is evaporated under reduced pressure and theresulting residue is purified by silica gel column chromatography(eluent; ethyl acetate:n-hexane=1:1→dichloromethane:methanol:aqueousammonia=60 10:1) to give5-hydroxymethyl-5-methylamino-1-[4-(2-methylbenzoylamino]benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(A; 35.3 mg) and5-methylaminomethyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(B; 109 mg).

(A); Colorless amorphous

¹ H-NMR(CDCl₃) δ; 1.50-2.10 (3H, m), 2.10-2.28 (1H, m), 2.36 (3H, s),2.48 (3H, s), 2.68-2.97 (1H, m), 3.26-3.47 (1H, m), 4.16 (1H, d, J=13.8Hz), 4.25 (1H, d, J=13.8 Hz), 5.95 (1H, brs), 6.60-6.76 (1H, m),6.97-7.52 (8H, m), 7.52-7.73 (2H, m), 7.73-7.97 (2H, m)

(B); White powder (recrystallized from ethyl acetate/n-hexane)

m.p. 176-179° C.

EXAMPLE 769

5-Methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1 g) is dissolved in dimethylformamide (10 ml) and thereto are addedpotassium carbonate (0.5 g) and ethyl iodide (0.45 g). The mixture isstirred at room temperature overnight. After completion of the reaction,the reaction solution is poured into ice-water and the precipitatedcrystal is collected by filtration, and purified by silica gel columnchromatography (eluent; dichloromethane:methanol=90:1), andrecrystallized from diisopropyl alcohol/petroleum ether to give5-(N-methyl-N-ethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(50 mg) as white powder, m.p. 192-193° C.

Using the suitable starting materials, the compounds of the aboveExamples 244, 246-248, 330, 339, 342, 346, 350, 366, 375, 376, 406-418,453, 455, 457, 460, 464, 467, 506, 507, 537-545, 547, 549-556, 561-566,568-571, 577, 601-603, 607-625, 654-672, 675, 677-681, 691-695, 697,698, 701-705, 707, 708, 712, 713, 715, 716, 719, 720 and 722-725 areobtained in the same manner as in Example 769.

EXAMPLE 770

To a suspension of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(3 g) in methanol (30 ml) are added potassium carbonate (1.5 g) andepichlorohydrine (5.7 ml), and the mixture is refluxed for 3 hours. Thesolvent is distilled off and to the resulting residue is added water andextracted three times with dichloromethane. The extract is washed withsaturated saline solution and dried over magnesium sulfate. Theresulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=80:1) to give5-(N-methyl-N-oxiranylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(C; 1.92 g) and5-[N-methyl-N-(2-hydroxy-3-methoxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(D; 0.38 g).

(C); Colorless needles (recrystallization from ethyl acetate)

m.p. 239-240° C.

(D); Colorless amorphous

¹ H-NMR(CDCl₃) δ; 1.35-4.55 (22H, m), 6.3-7.8 (13H, m)

EXAMPLE 771

5-[N-Methyl-N-oxiranylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.5 g) is dissolved in methanol (10 ml) and thereto is addeddiethylamine (0.13 ml). The mixture is refluxed for 3 hours. Aftercompletion of the reaction, the solvent is distilled off and theresulting residue is purified by silica gel column chromatography(eluent; dichloromethane methanol=30:1→dichloromethane:methanol:aqueousammonia=9:1:0.1) to give5-[N-methyl-N-(2-hydroxy-3-diethylaminopropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.38 g) as colorless amorphous.

¹ H-NMR(CDCl₃) δ; 1.10 (6H, t, J=7 Hz), 1.35-5.1 (23H, m), 6.55-7.8(13H, m)

EXAMPLE 772

A solution of5-hydroxyimino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.06 g) in acetic anhydride (10 ml) and pyridine (10 ml) is stirred atroom temperature overnight. After completion of the reaction, thereaction solution is concentrated. To the resulting residue is addedwater and the mixture is extracted with dichloromethane. The extract iswashed with saturated saline solution and dried over magnesium sulfate.The solvent is distilled off and the resulting residue is purified bysilica gel column chromatography (eluent;dichloromethane:methanol=80:1), and recrystallized fromethanol/petroleum ether to give5-acetyloxyimino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.75 g) as colorless prisms, m.p. 142-144° C.

EXAMPLE 773

Using the suitable starting materials, the compounds of the aboveExamples 671 and 672 are obtained in the same manner as in Example 380.

EXAMPLE 774

Using the suitable starting materials, the compounds of the aboveExamples 674, 699, 700, 706, 718 and 730 are obtained in the same manneras in Example 384.

EXAMPLE 775

Using the suitable starting materials, the compounds of the aboveExamples 654-672, 675, 677-687, 691-695, 697, 698, 701-705, 707, 708,712, 713, 715, 716 and 719-725 are obtained in the same manner as inExample 390.

EXAMPLE 776

Using the suitable starting materials, the compounds of the aboveExamples 654-672, 675, 677-679, 691-693, 698, 701-705, 707, 708, 712,713, 715, 716 and 719-725 are obtained in the same manner as in Example388.

EXAMPLE 777

Using the suitable starting materials, the compounds of the aboveExamples 705, 706 and 708 are obtained in the same manner as in Example394.

EXAMPLE 778

Using the suitable starting materials, the compound of the above Example671 is obtained in the same manner as in Example 397.

EXAMPLE 779

Using the suitable starting materials, the compound of the above Example672 is obtained in the same manner as in Example 402.

EXAMPLE 780

Using the suitable starting materials, the compound of the above Example726 is obtained in the same manner as in Example 634.

EXAMPLE 781

Using the suitable starting materials, the compound of the above Example740 is obtained in the same manner as in Examples 638 and 640.

EXAMPLE 782

Using the suitable starting materials, the compound of the above Example689 is obtained in the same manner as in Example 643.

EXAMPLE 783

Using the suitable starting materials, the compound of the above Example690 is obtained in the same manner as in Example 644.

EXAMPLE 784

Using the suitable starting materials, the following compound isobtained in the same manner as in Examples 1, 382, 388 and 390.

5-Dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride, colorless needles (recrystallized from ethanol/water),m.p. 233-237° C.

REFERENCE EXAMPLE 13

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

5-(2-Chloroacetyloxy)-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 156-159° C. (recrystallized from ethylacetate/n-hexane)

5-(2-Dimethylaminoacetyloxy)-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 108-109° C. (recrystallized from ethylacetate/n-hexane)

5-Oxo-7-chloro-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 157.5-159.5° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-8-chloro-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 151.5-153.5° C. (recrystallized from diethylether/dichloromethane)

REFERENCE EXAMPLE 14

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

5-(2-Dimethylaminoacetyloxy)-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ; 1.63-1.98 (2H, m), 1.98-2.25 (1H, m), 2.27 (3H, s),2.43 (3H, s), 2.65-3.23 (2H, m), 3.38 (2H, s), 3.67 (2H, brs), 4.77-5.28(1H, m), 6.04-6.31 (1H, m), 6.31-6.56 (2H, m), 6.58-6.86 (1H, m),6.86-7.46 (5H, m)

5-Oxo-7-chloro-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 193-193.5° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-8-chloro-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 171-174° C. (recrystallized from diethylether/dichloromethane)

REFERENCE EXAMPLE 15

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

5-Dimethylaminocarbonylmethoxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 129-131° C. (recrystallized from ethylacetate/n-hexane)

6-Oxo-1-(4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine, yellowneedles

¹ H-NMR (CDCl₃) δ; 1.65-2.3 (4H, m), 2.5-5.2 (4H, m), 6.7-6.9 (1H, m),7.27-7.5 (4H, m), 7.90-8.15 (3H, m)

6-Chloro-5-oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 198-202° C. (recrystallized fromdichloromethane/diethyl ether)

REFERENCE EXAMPLE 16

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

5-Dimethylaminocarbonylmethoxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ; 1.52-2.10 (3H, m), 2.10-3.20 (2H, m), 2.97 (3H, s),3.05 (3H, s), 4.03-4.48 (2H, m), 4.50-5.35 (2H, m), 6.26-6.57 (2H, m),6.57-6.88 (1H, m), 6.88-7.76 (5H, m)

6-Oxo-1-(4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine, light yellowamorphous

¹ H-NMR (CDCl₃) δ; 1.7-2.2 (4H, m), 2.5-5.2 (6H, m), 6.42 (2H, d, J=8.7Hz), 6.75-6.9 (1H, m), 7.05-7.4 (4H, m), 7.95-8.1 (1H, m)

6-Chloro-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 166-169° C. (recrystallized fromdichloromethane/diethyl ether)

9-Chloro-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder, m.p. 192.5-195° C. (recrystallized fromdichloromethane/diethyl ether)

REFERENCE EXAMPLE 17

5-Dimethylamino-1-(2-methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(86.0 g) is dissolved in ethanol (800 ml), and thereto is added platinumoxide (10 g). The mixture is subjected to hydrogenation at ordinarytemperature under atmospheric pressure of hydrogen for 4 hours. Thecatalyst is removed by filtration, and the solvent is distilled off. Theresulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=200:1→100:1), and further purified bysilica gel thin layer chromatography (developer;chloroform:methanol=10:1), and recrystallized from methanol/diethylether to give5-dimethylamino-1-(2-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(G) (Rf: 0.52, 27.4 g) and5-dimethylamino-1-(2-methyl-4-amino-benzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(H) (Rf: 0.48, 12.3 g).

(G): White powder

M.p. 154-156° C.; [α]_(D) ²² =0° (c=1.0, chloroform)

¹ H-NMR (CDCl₃) δ; 1.10-1.50 (1H, m), 1.50-2.00 (1H, m), 2.00-2.35 (11H,m), 2.90-5.18 (5H, m), 6.00-6.76 (3H, m), 6.81-7.64 (4H, m)

(H): White powder

M.p. 169.5-170° C.; [α]_(D) ²² =0° (c=1.5, chloroform)

¹ H-NMR (CDCl₃) δ; 1.11-2.90 (13H, m), 2.91-5.23 (5H, m), 6.15-6.53 (1H,m), 6.57-7.62 (6H, m)

Using the suitable starting materials, the compounds of the followingTable 5 are obtained in the same manner as in above Examples 1 and 382.

                  TABLE 5                                                         ______________________________________                                        1 #STR1583##                                                                  ______________________________________                                        Example 785                                                                     Structure                                                                      -                                                                          2  STR1584##                                                                     -                                                                          3  STR1585##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 174-175° C.                                             Form: Free                                                                    Example 786                                                                   Structure                                                                      -                                                                          4  STR1586##                                                                     -                                                                          5  STR1587##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 176-178° C.                                             Form: Free                                                                    Example 787                                                                   Structure                                                                      -                                                                          6  STR1588##                                                                     -                                                                          7  STR1589##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethyl acetate/petroleum ether                      Melting Point: 154.5-155° C.                                           Form: Free                                                                    Example 788                                                                   Structure                                                                      -                                                                          8  STR1590##                                                                     -                                                                          9  STR1591##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 138)                                                            Form: Free                                                                    Example 789                                                                   Structure                                                                      -                                                                          0  STR1592##                                                                     -                                                                          1  STR1593##                                                                     - Crystalline form: Colorless scales                                         Recrystallization solvent: Ethanol                                            Melting Point: 197-198° C.                                             Form: Free                                                                    Example 790                                                                   Structure                                                                      -                                                                          2  STR1594##                                                                     -                                                                          3  STR1595##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 248-249° C.                                             Form: Free                                                                    Example 791                                                                   Structure                                                                      -                                                                          4  STR1596##                                                                     -                                                                          5  STR1597##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/n-hexane                                   Melting Point: 162-163° C.                                             Form: Free                                                                    Example 792                                                                   Structure                                                                      -                                                                          6  STR1598##                                                                     -                                                                          7  STR1599##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol/petroleum ether                            Melting Point: 235-236.5° C.                                           Form: Free                                                                    Example 793                                                                   Structure                                                                      -                                                                          8  STR1600##                                                                     -                                                                          9  STR1601##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 139)                                                            Form: Free                                                                    Example 794                                                                   Structure                                                                      -                                                                          0  STR1602##                                                                     -                                                                          1  STR1603##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Dioxane                                            Melting Point: 269-271° C.                                             Form: Free                                                                    Example 795                                                                   Structure                                                                      -                                                                          2  STR1604##                                                                     -                                                                          3  STR1605##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Dimethylformamide                                  Melting Point: 286-287° C.                                             Form: Free                                                                    Example 796                                                                   Structure                                                                      -                                                                          4  STR1606##                                                                     -                                                                          5  STR1607##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Acetonitrile                                       Melting Point: 227-228° C.                                             Form: Free                                                                    Example 797                                                                   Structure                                                                      -                                                                          6  STR1608##                                                                     -                                                                          7  STR1609##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 140)                                                            Form: Free                                                                    Example 798                                                                   Structure                                                                      -                                                                          8  STR1610##                                                                     -                                                                          9  STR1611##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethyl acetate/petroleum ether                      Melting Point: 167-168° C.                                             Form: Free                                                                    Example 799                                                                   Structure                                                                      -                                                                          0  STR1612##                                                                     -                                                                          1  STR1613##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 141)                                                            Example 800                                                                   Structure                                                                      -                                                                          2  STR1614##                                                                     -                                                                          3  STR1615##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Diethyl ether                                      Melting Point: 164-171° C.                                             Form: K.sup.⊕                                                             Example 801                                                                   Structure                                                                      -                                                                          4  STR1616##                                                                     -                                                                          5  STR1617##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 142)                                                            Form: Free                                                                    Example 802                                                                   Structure                                                                      -                                                                          6  STR1618##                                                                     -                                                                          7  STR1619##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 143)                                                            Form: Free                                                                    Example 803                                                                   Structure                                                                      -                                                                          8  STR1620##                                                                     -                                                                          9  STR1621##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 144)                                                            Form: Free                                                                    Example 804                                                                   Structure                                                                      -                                                                          0  STR1622##                                                                     -                                                                          1  STR1623##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 145)                                                            Form: Free                                                                    Example 805                                                                   Structure                                                                      -                                                                          2  STR1624##                                                                     -                                                                          3  STR1625##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 207-208° C.                                             Form: Free                                                                    Example 806                                                                   Structure                                                                      -                                                                          4  STR1626##                                                                     -                                                                          5  STR1627##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 187-189° C.                                             Form: Free                                                                    Example 807                                                                   Structure                                                                      -                                                                          6  STR1628##                                                                     -                                                                          7  STR1629##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol/petroleum ether                            Melting Point: 217-218° C.                                             Form: Free                                                                    Example 808                                                                   Structure                                                                      -                                                                          8  STR1630##                                                                     -                                                                          9  STR1631##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate                                      Melting Point; 170-171° C.                                             Form: Free                                                                    Example 809                                                                   Structure                                                                      -                                                                          0  STR1632##                                                                     -                                                                          1  STR1633##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 239.5-241° C.                                           Form: Free                                                                    Example 810                                                                   Structure                                                                      -                                                                          2  STR1634##                                                                     -                                                                          3  STR1635##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 190-191° C.                                             Form: Free                                                                    Example 811                                                                   Structure                                                                      -                                                                          4  STR1636##                                                                     -                                                                          5  STR1637##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Diethyl ether                                      Melting Point: 163-163.5° C.                                           Form: Free                                                                    Example 812                                                                   Structure                                                                      -                                                                          6  STR1638##                                                                     -                                                                          7  STR1639##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 208-210° C.                                             Form: Free                                                                    Example 813                                                                   Structure                                                                      -                                                                          8  STR1640##                                                                     -                                                                          9  STR1641##                                                                     - Crystalline form: White powder                                             NMR analysis: 146)                                                            Form: Free                                                                    Example 814                                                                   Structure                                                                      -                                                                          0  STR1642##                                                                     -                                                                          1  STR1643##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 147)                                                            Form: Free                                                                    Example 815                                                                   Structure                                                                      -                                                                          2  STR1644##                                                                     -                                                                          3  STR1645##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/n-hexane                                   Melting Point: 250-252° C.                                             Form: Free                                                                    Example 816                                                                   Structure                                                                      -                                                                          4  STR1646##                                                                     -                                                                          5  STR1647##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethyl acetate                                      Melting Point: 214-216° C.                                             Form: Free                                                                    Example 817                                                                   Structure                                                                      -                                                                          6  STR1648##                                                                     -                                                                          7  STR1649##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol/n-hexane                                   Melting Point: 243-245° C.                                             Form: Free                                                                    Example 818                                                                   Structure                                                                      -                                                                          8  STR1650##                                                                     -                                                                          9  STR1651##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Diethyl ether                                      Melting Point: 159-162° C.                                             Form: Free                                                                    Example 819                                                                   Structure                                                                      -                                                                          0  STR1652##                                                                     -                                                                          1  STR1653##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 148)                                                            Form: Free                                                                    Example 820                                                                   Structure                                                                      -                                                                          2  STR1654##                                                                     -                                                                          3  STR1655##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethyl acetate                                      Melting Point: 287-289° C.                                             Form: Free                                                                    Example 821                                                                   Structure                                                                      -                                                                          4  STR1656##                                                                     -                                                                          5  STR1657##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Diethyl ether                                      Melting Point: 170-171° C.                                             Form: Free                                                                    Example 822                                                                   Structure                                                                      -                                                                          6  STR1658##                                                                     -                                                                          7  STR1659##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 204-205° C.                                             Form: Free                                                                    Example 823                                                                   Structure                                                                      -                                                                          8  STR1660##                                                                     -                                                                          9  STR1661##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 273-273.5° C.                                           Form: Free                                                                    Example 824                                                                   Structure                                                                      -                                                                          0  STR1662##                                                                     -                                                                          1  STR1663##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 149)                                                            Form: Free                                                                    Example 825                                                                   Structure                                                                      -                                                                          2  STR1664##                                                                     -                                                                          3  STR1665##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 240-241° C.                                             Form: Free                                                                    Example 826                                                                   Structure                                                                      -                                                                          4  STR1666##                                                                     -                                                                          5  STR1667##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Acetonitrile/ethanol                               Melting Point: 231-232° C.                                             Form: Free                                                                    Example 827                                                                   Structure                                                                      -                                                                          6  STR1668##                                                                     -                                                                          7  STR1669##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Acetonitrile/ethanol                               Melting Point: 222-224° C.                                             Form: Free                                                                    Example 828                                                                   Structure                                                                      -                                                                          8  STR1670##                                                                     -                                                                          9  STR1671##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 235-237° C.                                             Form: Free                                                                    Example 829                                                                   Structure                                                                      -                                                                          0  STR1672##                                                                     -                                                                          1  STR1673##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 150)                                                            Form: Free                                                                    Example 830                                                                   Structure                                                                      -                                                                          2  STR1674##                                                                     -                                                                          3  STR1675##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 151)                                                            Form: Free                                                                    Example 831                                                                   Structure                                                                      -                                                                          4  STR1676##                                                                     -                                                                          5  STR1677##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 152)                                                            Form: Free                                                                    Example 832                                                                   Structure                                                                      -                                                                          6  STR1678##                                                                     -                                                                          7  STR1679##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 153)                                                            Form: Free                                                                    Example 834                                                                   Structure                                                                      -                                                                          8  STR1680##                                                                     -                                                                          9  STR1681##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 247-248° C.                                             Form: Free                                                                    Example 835                                                                   Structure                                                                      -                                                                          0  STR1682##                                                                     -                                                                          1  STR1683##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 154)                                                            Form: Free                                                                    Example 836                                                                   Structure                                                                      -                                                                          2  STR1684##                                                                     -                                                                          3  STR1685##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 155)                                                            Form: Free                                                                    Example 837                                                                   Structure                                                                      -                                                                          4  STR1686##                                                                     -                                                                          5  STR1687##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 156)                                                            Form: Free                                                                    Example 838                                                                   Structure                                                                      -                                                                          6  STR1688##                                                                     -                                                                          7  STR1689##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 157)                                                            Form: Free                                                                    Example 839                                                                   Structure                                                                      -                                                                          8  STR1690##                                                                     -                                                                          9  STR1691##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 234-235° C.                                             Form: Free                                                                    Example 840                                                                   Structure                                                                      -                                                                          0  STR1692##                                                                     -                                                                          1  STR1693##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 234-235° C.                                             Form: Free                                                                    Example 841                                                                   Structure                                                                      -                                                                          2  STR1694##                                                                     -                                                                          3  STR1695##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 226-228° C.                                             Form: Free                                                                    Example 842                                                                   Structure                                                                      -                                                                          4  STR1696##                                                                     -                                                                          5  STR1697##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 230-231° C.                                             Form: Free                                                                    Example 843                                                                   Structure                                                                      -                                                                          6  STR1698##                                                                     -                                                                          7  STR1699##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 186-188° C.                                             Form: Free                                                                    Example 844                                                                   Structure                                                                      -                                                                          8  STR1700##                                                                     -                                                                          9  STR1701##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Chloroform/methanol                                Melting Point: 286-290° C.                                             Form: Free                                                                    Example 845                                                                   Structure                                                                      -                                                                          0  STR1702##                                                                     -                                                                          1  STR1703##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 186-188.5° C.                                           Form: Free                                                                    Example 846                                                                   Structure                                                                      -                                                                          2  STR1704##                                                                     -                                                                          3  STR1705##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 220-222° C.                                             Form: Free                                                                    Example 847                                                                   Structure                                                                      -                                                                          4  STR1706##                                                                     -                                                                          5  STR1707##                                                                     - Crystalline form: White powder                                             NMR analysis: 158)                                                            Form: Free                                                                    Example 848                                                                   Structure                                                                      -                                                                          6  STR1708##                                                                     - R.sup.3 : 4-NHCOCH.sub.2 CONH.sub.2                                        Crystalline form: Colorless prisms                                            Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 189-192° C.                                             Form: Free                                                                    Example 849                                                                   Structure                                                                      -                                                                          7  STR1709##                                                                     -                                                                          8  STR1710##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 159)                                                            Form: Free                                                                    Example 850                                                                   Structure                                                                      -                                                                          9  STR1711##                                                                     -                                                                          0  STR1712##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 207-209° C. (decomposed)                                Form: Free                                                                    Example 851                                                                   Structure                                                                      -                                                                          1  STR1713##                                                                     -                                                                          2  STR1714##                                                                     - Crystalline form: White powder                                             NMR analysis: 160)                                                            Form: K.sup.⊕                                                             Example 852                                                                   Structure                                                                      -                                                                          3  STR1715##                                                                     -                                                                          4  STR1716##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 193-194° C.                                             Form: Free                                                                    Example 853                                                                   Structure                                                                      -                                                                          5  STR1717##                                                                     -                                                                          6  STR1718##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 185.5-186° C.                                           Form: Free                                                                    Example 854                                                                   Structure                                                                      -                                                                          7  STR1719##                                                                     -                                                                          8  STR1720##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 223.5-226° C. (decomposed)                              Form: Free                                                                    Example 855                                                                   Structure                                                                      -                                                                          9  STR1721##                                                                     -                                                                          0  STR1722##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 161)                                                            Form: Free                                                                    Example 856                                                                   Structure                                                                      -                                                                          1  STR1723##                                                                     -                                                                          2  STR1724##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 225.5-227° C.                                           Form: Free                                                                    Example 857                                                                   Structure                                                                      -                                                                          3  STR1725##                                                                     -                                                                          4  STR1726##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 212-214° C.                                             Form: Free                                                                    Example 858                                                                   Structure                                                                      -                                                                          5  STR1727##                                                                     -                                                                          6  STR1728##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 230.5-233° C.                                           Form: Free                                                                    Example 859                                                                   Structure                                                                      -                                                                          7  STR1729##                                                                     -                                                                          8  STR1730##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 212.5-215° C. (decomposed)                              Form: Free                                                                    Example 860                                                                   Structure                                                                      -                                                                          9  STR1731##                                                                     -                                                                          0  STR1732##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 192-194.5° C.                                           Form: Free                                                                    Example 861                                                                   Structure                                                                      -                                                                          1  STR1733##                                                                     -                                                                          2  STR1734##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 175-177° C.                                             Form: Free                                                                    Example 862                                                                   Structure                                                                      -                                                                          3  STR1735##                                                                     -                                                                          4  STR1736##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 208.5-209.5° C.                                         Form: Free                                                                    Example 863                                                                   Structure                                                                      -                                                                          5  STR1737##                                                                     -                                                                          6  STR1738##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 191-193.5° C.                                           Form: Free                                                                    Example 864                                                                   Structure                                                                      -                                                                          7  STR1739##                                                                     -                                                                          8  STR1740##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 204-205.5° C.                                           Form: Free                                                                    Example 865                                                                   Structure                                                                      -                                                                          9  STR1741##                                                                     -                                                                          0  STR1742##                                                                     - Crystalline form: Light yellow prisms                                      Recrystallization solvent: Ethanol                                            Melting Point: 221-223° C.                                             Form: Free                                                                    Example 866                                                                   Structure                                                                      -                                                                          1  STR1743##                                                                     -                                                                          2  STR1744##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethyl acetate                                      Melting Point: 171-173° C.                                             Form: Free                                                                    Example 867                                                                   Structure                                                                      -                                                                          3  STR1745##                                                                     -                                                                          4  STR1746##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethyl acetate                                      Melting Point: 185-187° C.                                             Form: Free                                                                    Example 868                                                                   Structure                                                                      -                                                                          5  STR1747##                                                                     -                                                                          6  STR1748##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 190-192° C.                                             Form: Free                                                                    Example 869                                                                   Structure                                                                      -                                                                          7  STR1749##                                                                     -                                                                          8  STR1750##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 175-177° C.                                             Form: Free                                                                    Example 870                                                                   Structure                                                                      -                                                                          9  STR1751##                                                                     -                                                                          0  STR1752##                                                                     - Crystalline form: Colorless powder                                         Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 148-151° C.                                             Form: Free                                                                    Example 871                                                                   Structure                                                                      -                                                                          1  STR1753##                                                                     -                                                                          2  STR1754##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 200-202° C.                                             Form: Free                                                                    Example 872                                                                   Structure                                                                      -                                                                          3  STR1755##                                                                     -                                                                          4  STR1756##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 200-202° C.                                             Form: Free                                                                    Example 873                                                                   Structure                                                                      -                                                                          5  STR1757##                                                                     -                                                                          6  STR1758##                                                                     - Crystalline form: Light yellow powder                                      Recrystallization solvent: Acetone                                            Melting Point: 235-238° C.                                             Form: Free                                                                    Example 874                                                                   Structure                                                                      -                                                                          7  STR1759##                                                                     -                                                                          8  STR1760##                                                                     - Crystalline form: Light yellow powder                                      Recrystallization solvent: Acetone                                            Melting Point: 198-201° C.                                             Form: Free                                                                    Example 875                                                                   Structure                                                                      -                                                                          9  STR1761##                                                                     -                                                                          0  STR1762##                                                                     - Crystalline form: Light yellow needles                                     Recrystallization solvent: Chloroform/ethyl acetate                           Melting Point: 232-237° C.                                             Form: Free                                                                    Example 876                                                                   Structure                                                                      -                                                                          1  STR1763##                                                                     -                                                                          2  STR1764##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Chloroform/ethyl acetate                           Melting Point: 224-227° C.                                             Form: Free                                                                    Example 877                                                                   Structure                                                                      -                                                                          3  STR1765##                                                                     -                                                                          4  STR1766##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 211-214° C.                                             Form: Free                                                                    Example 878                                                                   Structure                                                                      -                                                                          5  STR1767##                                                                     -                                                                          6  STR1768##                                                                     - Crystalline form: Colorless powder                                         Recrystallization solvent: Dichloromethane/n-hexane                           Melting Point: 238-243° C.                                             Form: Free                                                                    Example 879                                                                   Structure                                                                      -                                                                          7  STR1769##                                                                     -                                                                          8  STR1770##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 162)                                                            Form: Free                                                                    Example 880                                                                   Structure                                                                      -                                                                          9  STR1771##                                                                     -                                                                          0  STR1772##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 163)                                                            Form: Free                                                                    Example 881                                                                   Structure                                                                      -                                                                          1  STR1773##                                                                     -                                                                          2  STR1774##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 198-202° C.                                             Form: Free                                                                    Example 882                                                                   Structure                                                                      -                                                                          3  STR1775##                                                                     -                                                                          4  STR1776##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Chloroform/ethyl acetate                           Melting Point: 226-229° C.                                             Form: Free                                                                    Example 883                                                                   Structure                                                                      -                                                                          5  STR1777##                                                                     -                                                                          6  STR1778##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 139-140° C.                                             Form: Free                                                                    Example 884                                                                   Structure                                                                      -                                                                          7  STR1779##                                                                     -                                                                          8  STR1780##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 149-152° C.                                             Form: Free                                                                    Example 885                                                                   Structure                                                                      -                                                                          9  STR1781##                                                                     -                                                                          0  STR1782##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 180.5-182° C.                                           Form: Free                                                                    Example 886                                                                   Structure                                                                      -                                                                          1  STR1783##                                                                     -                                                                          2  STR1784##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Chloroform/diethyl ether                           Melting Point: 211-214° C.                                             Form: Free                                                                    Example 887                                                                   Structure                                                                      -                                                                          3  STR1785##                                                                     -                                                                          4  STR1786##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Chloroform/diethyl ether                           Melting Point: 171-174.5° C.                                           Form: Free                                                                    Example 888                                                                   Structure                                                                      -                                                                          5  STR1787##                                                                     -                                                                          6  STR1788##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 203-205° C.                                             Form: Free                                                                    Example 889                                                                   Structure                                                                      -                                                                          7  STR1789##                                                                     -                                                                          8  STR1790##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 202-202.5                                                      Form: Free                                                                    Example 890                                                                   Structure                                                                      -                                                                          9  STR1791##                                                                     -                                                                          0  STR1792##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 130-133° C.                                             Form: Free                                                                    Example 891                                                                   Structure                                                                      -                                                                          1  STR1793##                                                                     -                                                                          2  STR1794##                                                                     -                                                                          3  STR1795##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 104.5-106° C.                                           Form: Free                                                                    Example 892                                                                   Structure                                                                      -                                                                          4  STR1796##                                                                     -                                                                          5  STR1797##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 197-198° C.                                             Form: Free                                                                    Example 893                                                                   Structure                                                                      -                                                                          6  STR1798##                                                                     -                                                                          7  STR1799##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/ethyl acetate                      Melting Point: 191-192° C.                                             Form: Free                                                                    Example 894                                                                   Structure                                                                      -                                                                          8  STR1800##                                                                     -                                                                          9  STR1801##                                                                     - Crystalline form: Colorless columnar                                       Recrystallization solvent: Ethanol/petroleum ether                            Melting Point: 211-213° C.                                             Form: Free                                                                    Example 895                                                                   Structure                                                                      -                                                                          0  STR1802##                                                                     -                                                                          1  STR1803##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 164)                                                            Form: Free                                                                    Example 896                                                                   Structure                                                                      -                                                                          2  STR1804##                                                                     -                                                                          3  STR1805##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 165)                                                            Form: Free                                                                    Example 897                                                                   Structure                                                                      -                                                                          4  STR1806##                                                                     -                                                                          5  STR1807##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 166)                                                            Form: Free                                                                    Example 898                                                                   Structure                                                                      -                                                                          6  STR1808##                                                                     -                                                                          7  STR1809##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 224-228° C.                                             Form: Free                                                                  ______________________________________                                            138)    .sup.1 H-NMR(CDCl.sub.3)δ; 1.3-2.95(19H, m), 3.05-3.3(1H                ,                                                                    m), 3.85-4.1(2H, m), 4.3-4.6(1H, m), 6.64(1H, d,                              J=7.8Hz), 6.9-7.8(12H, m)                                                    139) .sup.1 H-NMR(CDCl.sub.3)δ; 1.1-2.3(13H, m), 2.65-3.2(1H,                       m), 4.55-5.6(3H, m), 6.55-6.7(1H, m), 6.9-7.6                      (12H, m)                                                                     140) .sup.1 H-NMR(CDCl.sub.3)δ; 1.3-4.15(19H, m), 4.3-5.0(1H,                       m), 6.65(1H, d, J=7.7Hz), 6.9-8.05(12H, m)                        141) .sup.1 H-NMR(CDCl.sub.3)δ; 1.4-3.0(9H, m), 3.05-3.6(3H,                        m), 3.9-4.1(1H, m), 4.35-4.55(1H, m), 4.9-5.65                     (1H, m), 6.67(1H, d, J=7.4Hz), 6.85-7.6(12H, m),                              7.6-7.85(2H, m)                                                              142) .sup.1 H-NMR(CDCl.sub.3)δ; 1.3-2.85(21H, m), 3.2-4.0(4H,                       m), 4.3-4.4(1H, m), 4.45-5.2(2H, m), 6.61(1H, d,                   J=7.6Hz), 6.9-7.65(12H, m)                                                   143) .sup.1 H-NMR(CDCl.sub.3)δ; 1.3-3.45(17H, m), 3.8-5.7(5H,                       m), 6.5-7.65(13H, m)                                              144) .sup.1 H-NMR(CDCl.sub.3)δ; 1.25-3.1(14H, m), 3.3-4.0(4H,                       m), 4.15-4.4(1H, m), 4.45-5.2(1H, m), 6.64(1H,                     d, J=7.4Hz), 6.9-7.7(12H, m)                                                 145) .sup.1 H-NMR(CDCl.sub.3)δ; 0.9-3.25(16H, m), 3.9-5.9(2H,                       m), 6.65(1H, d, J=7.4Hz), 6.85-7.5(11H, m), 7.9-                   8.3(1H, m)                                                                   146) .sup.1 H-NMR(DMSO-d.sub.6)δ; 1.3-2.15(4H, m), 2.32(3H,                         s), 2.8-3.05(1H, m), 4.24(2H, AB-q, J=12.8, 15.4                   Hz), 4.35-4.55(1H, m), 4.9-5.25(1H, m), 6.68(1H,                              d, J=7.6Hz), 6.9-7.45(9H, m), 7.52(2H, d, J=8.6                               Hz), 8.9-9.05(1H, m), 10.31(1H, s)                                           147) .sup.1 H-NMR(CDCl.sub.3)δ; 1.5-2.35(4H, m), 2.45(3H, s),                       2.6-2.85(1H, m), 3.32(3H, s), 4.19(2H, AB-q,                       J=12.2Hz, 15.6Hz), 5.0-5.2(1H, m), 5.82(1H, d,                                J=10.3Hz), 6.69(1H, d, J=7.8Hz), 6.75-7.95(12H,                               m)                                                                           148) .sup.1 H-NMR(CDCl.sub.3)δ; 1.2-3.3(17H, m), 3.45(2H, AB-                       q, J=14.7, 22.9Hz), 3.9-4.35(2H, m), 6.60(2H, d,                   J=7.7Hz), 6.8-8.0(11H, m), 8.39(1H, s)                                       149) .sup.1 H-NMR(CDCl.sub.3)δ; 1.45-3.40(8H, m), 2.23(3H, s),                      2.33(3H, s), 2.46(3H, s), 4.44-5.23(1H, m),                        6.54-6.78(1H, m), 6.84-7.94(12H, m)                                          150) .sup.1 H-NMR(CDCl.sub.3)δ; 1.50-1.92(3H, m), 1.92-2.05                         (1H, m), 2.47(3H, s), 2.55-3.06(5H, m), 3.43-5.76                  (8H, m), 6.63-6.82(1H, m), 6.97-8.08(12H, m)                                 151) .sup.1 H-NMR(CDCl.sub.3)δ; 1.43-2.65(4H, m), 2.48(3H, s),                      2.69-3.25(5H, m), 3.90-5.40(8H, m), 6.64-6.94                      (1H, m), 6.94-7.77(12H, m)                                                   152) .sup.1 H-NMR(CDCl.sub.3)δ; 1.50-1.90(3H m), 1.90-2.20                          (1H, m), 2.20-2.64(4H, m), 2.32(3H, s), 2.47(3H,                   s), 2.64-3.27(1H, m), 3.36-3.83(4H, m), 3.93--4.52                            (2H, m), 4.52-5.27(2H, m), 6.57-6.82(1H, m),                                  6.93-7.87(12H, m)                                                            153) .sup.1 H-NMR(CDCl.sub.3)δ; 1.52-1.93(2H, m), 1.93-2.23                         (4H, m), 2.23-2.57(1H, m), 2.45(3H, s), 2.72-3.02                  (1H, m), 3.02-3.77(8H, m), 3.93-4.50(2H, m),                                  4.50-5.20(2H, m), 6.60-6.80(1H, m), 6.94-7.64                                 (11H, m), 8.16(1H, brs)                                                      154) .sup.1 H-NMR(CDCl.sub.3)δ; 1.48-2.60(8H, m), 2.46(3H, s),                      2.65-3.01(1H, m), 3.20-3.74(2H, m), 3.80-5.14                      (4H, m), 5.30-5.84(1H, m), 6.51-8.14(13H, m)                                 155) .sup.1 H-NMR(CDCl.sub.3)δ; 1.54-1.91(2H, m), 1.91-2.20                         (1H, m), 2.22-2.64(1H, m), 2.44(3H, s), 2.70-3.13                  (1H, m), 3.60-4.40(4H, m), 4.50-5.20(2H, m),                                  6.07-8.00(13H, m), 9.93(1H, s)                                               156) .sup.1 H-NMR(CDCl.sub.3)δ; 1.56-1.92(2H, m), 1.92-2.19(1H,                     m), 2.19-2.60(1H, m), 2.46(3H, s), 2.66-3.26(4H,                   m), 3.33-3.95(4H, m). 4.00-5.20(4H, m), 6.58-6.82                             (1H, m), 6.93-8.21(12H, m)                                                   157) .sup.1 H-NMR(CDCl.sub.3)δ; 1.57-2.17(3H, m), 2.21-2.68                         (1H, m), 2.47(3H, s), 2.73-3.04(1H, m), 3.92-4.42                  (4H, m), 4.50-5.17(2H, m), 6.61-6.99(2H, m),                                  6.99-8.10(14H, m), 8.21-8.71(2H, m)                                          158) .sup.1 H-NMR(CDCl.sub.3)δ; 1.31(3H, d, J=6.7Hz), 1.53-                         1.90(1H, m), 2.29-2.58(1H, m), 2.47(3H, s),                        2.94-3.63(2H, m), 4.57-5.05(1H, m), 6.68-6.82                                 (1H, m), 7.10-7.59(10H, m), 7.72(1H, s), 7.78-                                7.96(1H, m)                                                                  159) .sup.1 H-NMR(CDCl.sub.3)δ; 1.20-2.60(17H, m), 2.65-5.10                        (3H, m), 6.85-3.85(12H, m)                                        160) .sup.1 H-NMR(DMSO-d.sub.6)δ; 1.40-1.75(1H, m), 1.90-2.15                       (1H, m), 2.33(3H, s), 2.50-2.80(2H, m), 3.10-3.50                  (1H, m), 4.40-4.65(1H, m), 6.85-7.60(10H, m),                                 7.85(1H, s), 10.44(1H, s)                                                    161) .sup.1 H-NMR(CDCl.sub.3)δ; 1.30-2.70(11H, m), 3.00-5.20                        (3H, m), 6.58(1H, d, J=8Hz), 6.90-7.05(1H, m),                     7.10-7.70(10H, m)                                                            162) .sup.1 H-NMR(CDCl.sub.3)δ; 1.25-2.90(4H, m), 2.44(6H, s),                      2.79-3.57(2H, m), 2.79(6H, s), 4.10-5.25(1H, m),                   6.60-6.80(1H, m), 6.94-7.60(10H, m), 8.23(1H, d,                              J=6.2Hz), 12.41(1H, m)                                                       163) .sup.1 H-NMR(CDCl.sub.3)δ; 1.25-3.00(4H, m), 2.42(6H, s),                      2.99(6H, s), 3.40-3.65(2H, m), 4.01-5.15(1H, m),                   6.58-7.59(12H, m), 7.94(1H, brs)                                             164) .sup.1 H-NMR(DMSO-d.sub.6)δ; 1.40-2.18(4H, m), 2.34(3H,                        s), 2.47(3H, s), 2.54-3.50(4H, m), 4.30-5.08(1H,                   m), 6.56-6.82(1H, m), 6.87-7.48(10H, m), 7.48-                                7.75(2H, m), 10.35(1H, s)                                                    165) .sup.1 H-NMR(CDCl.sub.3)δ; 1.08-5.20[20H, m, 1.30(3H, t,                       J=7.2Hz), 3.41(2H, s), 4.22(2H, q, J=7.2Hz)],                      6.49-7.73(8H, m), 9.25-9.58(1H, m)                                           166) .sup.1 H-NMR(CDCl.sub.3)δ; 1.17-2.80(4H, m), 2.05(3H, s),                      2.42(6H, s), 3.02-3.53(2H, m), 4.06-5.15(1H, m),                   6.55-7.80(12H, m), 8.53-8.74(2H, m)                                        ______________________________________                                    

EXAMPLE 899

To a solution of5-acetyloxyimino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.48 g) in acetic acid (20 ml) is added platinum oxide (0.05 9) and themixture is subjected to catalytic reduction under hydrogen atmosphere.After completion of the reaction, the catalyst is removed by filtration,and the filtrate is concentrated. The resulting residue is purified bysilica gel column chromatography (eluent;dichloromethane:methanol=20:1→10:1), and recrystallized fromethanol/diethyl ether to give5-amino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.19 g) as colorless prisms, m.p. 176-178° C.

EXAMPLE 900

To a solution of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dichloromethane (10 ml) is added triethylamine (0.24 ml).Subsequently, thereto is added methanesulfonyl chloride (0.14 ml) underice-cooling, and then, the mixture is warmed to room temperature andstirred overnight. Water is added to the reaction solution, extractedthree times with dichloromethane. The extract is washed with saturatedsaline solution, and dried over magnesium sulfate. The solvent isdistilled off and the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=20:1), andrecrystallized from ethanol to give5-(N-methyl-N-methanesulfonylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.48 9) as colorless scales, m.p. 197-198° C.

EXAMPLE 901

To a solution of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dichloromethane is added triethylamine (0.24 ml).Subsequently, thereto is added benzoyl chloride (0.2 ml) underice-cooling, and the temperature thereof is raised to room temperature,and the mixture is stirred overnight. Water is added to the reactionsolution and extracted three times with dichloromethane. The extract iswashed with saturated saline solution and dried over magnesium sulfate.The solvent is distilled off and the resulting residue is purified bysilica gel column chromatography (eluent;dichloromethane:methanol=20:1), and recrystallized from ethanol to give5-(N-methyl-N-benzoylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.64 g) as colorless needles, m.p. 248-249° C.

EXAMPLE 902

A mixture of5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) and ethyl formate (10 ml) is refluxed for 4 hours. The reactionsolution is concentrated and the resulting residue is recrystallizedfrom ethanol/petroleum ether to give5-formylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.38 g) as colorless columnar crystal, m.p. 211-213° C.

Using the suitable starting materials, the compounds of above Examples825 and 894 are obtained in the same manner as in above Example 902.

EXAMPLE 903

To a solution of5-amino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dichloromethane (10 ml) is added triethylamine (0.22 ml).Subsequently, thereto is added di-tert-butyl dicarbonate (0.34 g) atroom temperature and the mixture is stirred for 2 hours. Then, theretois added additional di-tert-butyl dicarbonate (0.1 g) and the mixture isstirred for 1 hour. The reaction mixture is concentrated and theresulting residue is purified by silica gel column chromatography(eluent; n-hexane:ethyl aceate=1:1) to give5-t-butoxycarbonylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.66 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.1-2.3 (13H, m), 2.65-3.2 (1H, m), 4.55-5.6 (3H, m),6.55-6.7 (1H, m), 6.9-7.6 (12H, m)

Using the suitable starting materials, the compound of above Example 791is obtained in the same manner as in above Example 903.

EXAMPLE 904

To a solution of5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dichloromethane (10 ml) is added phenyl isocyanate (0.2 g)under ice-cooling. The mixture is stirred at the same temperature for 30minutes, and the temperature thereof is raised to room temperature andthen the mixture is stirred overnight. The reaction solution isdistilled off and the resulting residue is recrystallized from dioxaneto give5-anilinocarbonylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.65 g) as colorless prisms, m.p. 269-271° C.

Using the suitable starting materials, the compound of above Example 795is obtained in the same manner as in above Example 904.

EXAMPLE 905

To a solution of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in methanol (10 ml) is added glycolonitrile (50%, 0.19 ml) andthe mixture is stirred at room temperature for 20 minutes, and thenrefluxed for 30 minutes. Thereto is added additional glycolonitrile (0.5ml) and the mixture is refluxed for 5.5 hours. The reaction solution isconcentrated and to the resulting residue is added ethyl acetate. Theprecipitated crystal is collected by filtration, and recrystallized fromacetonitrile to give5-(N-methyl-N-cyanomethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.32 g) as colorless needles, m.p. 227-228° C.

EXAMPLE 906

To5-(N-methyl-N-oxiranylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.62 g) is added trifluoroacetic acid (1.22 ml) under ice-cooling andthe mixture is stirred for 4 hours. The reaction solution is neutralizedwith aqueous sodium carbonate solution, and extracted three times withdichloromethane. The extract is washed with saturated saline solutionand dried over magnesium sulfate. The solvent is distilled off and theresulting residue is dissolved in methanol (10 ml). Thereto is added 40%aqueous sodium hydroxide solution (10 ml) and water (10 ml), and themixture is stirred at room temperature overnight. Methanol is distilledoff and the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=30:1) to give5-[N-methyl-N-(2,3-dihydroxypropyl)amino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.23 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.3-4.15 (19H, m), 4.3-5.0 (1H, m), 6.65 (1H, d,J=7.7 Hz), 6.9-8.05 (12H, m)

EXAMPLE 907

A mixture of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.64 g), acetonitrile (20 ml), potassium carbonate (0.6 g) and ethylbromoacetate (0.44 ml) is refluxed for 3 hours. The reaction solution isconcentrated and water is added to the resulting residue, and themixture is extracted three times with dichloromethane. The extract iswashed with saturated saline solution, and dried over magnesium sulfate.The solvent is distilled off and the resulting residue is purified bysilica gel column chromatography (eluent;dichloromethane:methanol=30:1), and recrystallized from ethylacetate/petroleum ether to give5-(N-methyl-N-ethoxycarbonylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.82 g) as colorless prisms, m.p. 167-168° C.

Using the suitable starting materials, the compounds of above Examples785, 787, 799, 800, 802-806, 808, 811, 819, 824, 826, 827, 845, 848,849, 850, 852, 855-858, 860, 861, 863-882, 885-893 and 895-898 areobtained in the same manner as in above Example 907.

EXAMPLE 908

5-(N-Methyl-N-ethoxycarbonylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) is dissolved in saturated solution of ammonia in methanol (20ml), and the mixture is heated at 100° C. for 8 hours in a sealed tube.The reaction solution is concentrated and the resulting residue ispurified by silica gel column chromatography (eluent;dichloromethane:methanol=30:1) to give5-(N-methyl-N-carbamoylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.4 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.4-3.0 (9H, m), 3.05-3.6 (3H, m), 3.9-4.1 (1H, m),4.35-4.55 (1H, m), 4.9-5.65 (1H, m), 6.67 (1H, d, J=7.4 Hz), 6.85-7.6(12H, m), 7.6-7.85 (2H, m)

EXAMPLE 909

To a solution of5-(N-methyl-N-ethoxycarbonylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dioxane (10 ml) is added aqueous solution (1 ml) of sodiumhydroxide (0.07 g) and the mixture is stirred at room temperature for 2days. The reaction solution is concentrated and to the resulting residueis added water. The insoluble materials are removed by filtration. Thefiltrate is neutralized with 10% hydrochloric acid and extracted threetimes with dichloromethane. The extract is washed with saturated salinesolution and dried over magnesium sulfate. The solvent is distilled offand to the resulting residue is added a solution of potassiumethylhexanoate (0.2 g) in dichloromethane (20 ml). The solvent isdistilled off, and diethyl ether is added to the resulting residue. Theprecipitated crystal is collected by filtration, and recrystallized fromdiethyl ether to give potassium2-[N-methyl-N-{1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin-5-yl}amino]acetate(0.6 g) as colorless needles, m.p. 164-171° C.

EXAMPLE 910

To a solution of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.5 g) in dimethyformamide (20 ml) are added potassium carbonate (0.6g), potassium iodide (0.72 g) and2-(3-bromopropyloxy)-3,4,5,6-tetrahydro-2H-pyrane (0.97 g) and themixture is stirred at room temperature overnight. The reaction solutionis concentrated and to the resulting residue is added water. The mixtureis extracted three times with dichloromethane. The extract is washedwith saturated saline solution, and dried over magnesium sulfate. Thesolvent is distilled off and the resulting residue is purified by silicagel column chromatography (eluent;dichloromethane→dichloromethane:methanol=50:1) to give5-{N-methyl-N-[3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propyl]amino}-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.3 g) as colorless amorphous.

¹ H-NMR (CDCl₃); 1.3-2.85 (21H, m), 3.2-4.0 (4H, m), 4.3-4.4 (1H, m),4.45-5.2 (2H, m), 6.61 (1H, d, J=7.6 Hz), 6.9-7.65 (12H, m)

EXAMPLE 911

To5-{N-methyl-N-[3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propyl]amino}-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.4 g) is added a mixture of acetyl chloride (0.5 ml) and acetic acid(5 ml) at room temperature, and the mixture is stirred overnight. Thereaction solution is concentrated and the resulting residue is purifiedby silica gel column chromatography (eluent;dichloromethane:methanol=30:1), and further purified again by silica gelcolumn chromatography (eluent; n-hexane:ethyl acetate=1:2) to give5-[N-methyl-N-(3-acetyloxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.06 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.3-3.45 (17H, m), 3.8-5.7 (5H, m), 6.5-7.65 (13H, m)

EXAMPLE 912

To a solution of5-{N-methyl-N-[3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propyl]amino}-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.55 g) in ethanol (10 ml) is added pyridinium p-toluenesulfonate (0.03g) and the mixture is heated at 60° C. overnight. After the mixture isrefluxed for more 2 hours, water and pyridinium p-toluenesulfonate (0.03g) are added thereto. The mixture is refluxed for 4 hours. The reactionsolution is concentrated and to the resulting residue is addeddichloromethane. The mixture is basified with aqueous sodium hydrogencarbonate solution and extracted three times with dichloromethane. Theextract is washed with saturated saline solution and dried overmagnesium sulfate. The solvent is distilled off and the resultingresidue is purified by silica gel column chromatography (eluent;dichloromethane:methanol=30:1) to give5-[N-methyl-N-(3-hydroxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.26 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.25-3.1 (14H, m), 3.3-4.0 (4H, m), 4.15-4.4 (1H, m),4.45-5.2 (1H, m), 6.64 (1H, d, J=7.4 Hz), 6.9-7.7 (12H, m)

EXAMPLE 913

To a solution of5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in acetic acid (10 ml) is added dropwise2,5-dimethoxytetrahydrofuran (0.19 ml), and the mixture is refluxed for1 hour. The reaction solution is concentrated and the resulting residueis purified by silica gel column chromatography (eluent;dichloromethane:methanol=50:1), and recrystallized from ethylacetate/n-hexane to give5-(1-pyrrolyl)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.31 g) as colorless prisms, m.p. 208-210° C.

EXAMPLE 914

To a solution of5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2.5 g) in dichloromethane (30 ml) is added triethylamine (0.96 ml) andfurther thereto is added dropwise chloroacetyl chloride (0.55 ml) underice-cooling. The mixture is stirred for 5 minutes. The reaction solutionis concentrated and to the resulting residue is added water. Theprecipitated crystal is collected by filtration, washed with water, anddried to give5-(2-chloroacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.4 g) as white powder.

¹ H-NMR (DMSO-d₆) δ; 1.3-2.15 (4H, m), 2.32 (3H, s), 2.8-3.05 (1H, m),4.24 (2H, AB-q, J=12.8, 15.4 Hz), 4.35-4.55 (1H, m), 4.9-5.25 (1H, m),6.68 (1H, d, J=7.6 Hz), 6.9-7.45 (9H, m), 7.52 (2H, d, J=8.6 Hz),8.9-9.05 (1H, m), 10.31 (1H, s)

Using the suitable starting materials, the compound of above Example 814is obtained in the same manner as in above Example 914.

EXAMPLE 915

A mixed solution of5-(2-chloroacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g), imidazole (0.1 g) and potassium carbonate (0.19 g) inacetonitrile (30 ml) is refluxed for 8 hours. The reaction solution isconcentrated and the resulting residue is washed with water andseparated by decantation. The remainder is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=20:1→15:1), andrecrystallized from ethanol/n-hexane to give5-[2-(1-imidazolyl)acetylamino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.15 g) as colorless needles, m.p. 250-252° C.

Using the suitable starting materials, the compound of above Example 818is obtained in the same manner as in above Example 915.

EXAMPLE 916

To a solution of5-(2-chloroacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dimethylformamide (20 ml) are added dimethylaminehydrochloride (0.21 g) and potassium carbonate (0.54 g), and the mixtureis stirred at room temperature for 2 days. The reaction solution isconcentrated and water is added to the resulting residue. Theprecipitated crystal is collected by filtration, and recrystallized fromethyl acetate to give5-(2-dimethylaminoacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.24 g) as colorless prisms, m.p. 214-216° C.

Using the suitable starting materials, the compounds of above Examples816, 817, 820, 821, 826 and 827 are obtained in the same manner as aboveExample 916.

EXAMPLE 917

A mixture of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g), N,N-dimethyl-2-chloroacetamide (0.19 g) and potassium carbonate(0.22 g) is refluxed for 24 hours. The reaction solution is concentratedand water is added to the resulting residue. The mixture is extractedthree times with dichloromethane. The extract is washed with saturatedsaline solution, and dried over magnesium sulfate. The solvent isdistilled off and the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=30:1) to give5-[N-methyl-N-(dimethylaminocarbonylmethyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.05 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.2-3.3 (17H, m), 3.45 (2H, AB-q, J=14.7, 22.9 Hz),3.9-4.35 (2H, m), 6.60 (1H, d, J=7.7 Hz), 6.8-8.0 (11H, m), 8.39 (1H, s)

EXAMPLE 918

To a solution of t-butoxycarbonylglycine (0.84 g) in dimethylformamide(20 ml) are added diethyl cyanophosphate (0.73 ml) and5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.74 g), and further thereto is added triethylamine (1.8 ml) underice-cooling. The mixture is stirred for 30 minutes, and then stirred atroom temperature overnight. The reaction solution is concentrated andwater is added to the resulting residue. The precipitated crystal iscollected by filtration, washed with water, and recrystallized fromethyl acetate to give5-(2-aminoacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(E) (0.16 g). Separately, the filtrate is concentrated and purified bysilica gel column chromatography (eluent;dichloromethane:methanol=50:1), and recrystallized from diethyl ether togive5-[2-(t-butoxycarbonylamino)acetylamino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(F) (0.19 g).

(E): Colorless prisms, m.p. 287-289° C.

(F): Colorless prisms, m.p. 170-171° C.

EXAMPLE 919

5-Oxo-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.50 g) is suspended in tetrahydrofuran (20 ml), and thereto is addeddropwise a 3.0 M solution of methyl magnesium bromide in diethyl ether(1.5 ml) at room temperature. The mixture is stirred at room temperaturefor 1 hour. The reaction solution is poured into ice-water (20 ml), andextracted with ethyl acetate. The extract is dried over magnesiumsulfate, and the solvent is distilled off. The resulting residue ispurified by silica gel column chromatography (eluent; ethylacetate:n-hexane=2:3→1:1), and recrystallized from ethylacetate/n-hexane to give5-methyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.23 g) as white powder, m.p. 204-205° C.

EXAMPLE 920

To a solution of5-carboxymethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.50 g) in dimethylformamide (60 ml) are added successivelythiomorpholine (0.66 ml), diethyl cyanophosphate (0.89 g) andtriethylamine (1.37 ml) with stirring under ice-cooling. The mixture isstirred for 30 minutes under ice-cooling, and at room temperature for 20minutes. Water (60 ml) is added to the reaction solution, and extractedwith dichloromethane. The extract is dried over magnesium sulfate, andthe solvent is distilled off. The resulting residue is purified bysilica gel column chromatography (eluent; ethylacetate:n-hexane=5:2→3:1), and recrystallized from ethylacetate/n-hexane to give5-(thiomorpholinocarbonylmethoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.60 g) as white powder, m.p. 235-237° C.

Using the suitable starting materials, the compounds of above Examples829-838 are obtained in the same manner as in above Example 920.

EXAMPLE 921

To a solution of5-(thiomorpholinocarbonylmethoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.40 g) in dichloromethane (40 ml) is added 80% m-chloroperbenzoic acid(175 mg) with stirring at -8° C., and the mixture is stirred at -8° C.for 1 hour. To the reaction solution is added 20% aqueous sodiumhydrogensulfite solution (40 ml) and the mixture is stirred at roomtemperature for 30 minutes. The dichloromethane layer is collected,washed with saturated saline solution and dried over magnesium sulfate.The solvent is distilled off and the resulting residue is purified bysilica gel column chromatography (eluent; dichloromethane:methanol=20:1)to give5-[(1-oxothiomorpholino)carbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.32 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.50-1.92 (3H, m), 1.92-2.05 (1H, m), 2.47 (3H, s),2.55-3.06 (5H, m), 3.43-5.76 (8H, m), 6.63-6.82 (1H, m), 6.97-8.08 (12H,m)

EXAMPLE 922

To a solution of5-(thiomorpholinocarbonylmethoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.40 g) in dichloromethane (40 ml) is added 80% m-chloroperbenzoic acid(0.35 g), and the mixture is stirred at room temperature for 1 hour. Thereaction solution is washed successively with an aqueous sodiumhydrogensulfite solution and saturated saline solution, and dried overmagnesium sulfate. The solvent is distilled off to give5-[(1,1-dioxothiomorpholino)carbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.41 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.43-2.65 (4H, m), 2,48 (3H, s), 2.69-3.25 (5H, m),3.90-5.40 (8H, m), 6.64-6.94 (1H, m), 6.94-7.77 (12H, m)

EXAMPLE 923

To a solution of5-oxo-1-[4-(2-hydroxybenzoylamino)benzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(400 mg) in acetone (20 ml) are added potassium carbonate (210 mg),potassium iodide (250 mg) and 2-chloroacetamide (120 mg), and themixture is refluxed for 2 hours. The insoluble materials are removed byfiltration, and the filtrate is distilled off. Dichloromethane is addedto the resulting residue, and the mixture is washed with saturatedsaline solution, and dried over magnesium sulfate. The solvent isdistilled off and the resulting residue is recrystallized from ethylacetate/n-hexane to give5-oxo-1-[4-(2-carbamoylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(436 mg) as white powder, m.p. 226-228° C.

Using the suitable starting materials, the compound of above Example 842is obtained in the same manner as above Example 923.

EXAMPLE 924

A mixture of5-methylamino-4-hydroxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.13 g), ethyl α-bromoacetate (58 mg), diisopropylethylamine (49 mg)and acetonitrile (5 ml) is refluxed for 10 hours. Acetonitrile isdistilled off under reduced pressure, and the resulting residue isdissolved in dichloromethane, washed with water, dried over magnesiumsulfate, and distilled off under reduced pressure. The resulting residueis purified by silica gel column chromatography (eluent;dichloromethane:methanol=50:1), and recrystallized fromchloroform/methanol to give7-[4-(2-chlorobenzoylamino)benzoyl]-1-methyl-1,2,3,4a,5,6,7,11b-octahydro-3-oxo[1]benzazepino[4,5-b][1,4]oxazine(80 mg) as colorless prisms, m.p. 286-290° C.

EXAMPLE 925

To a solution of5-oxo-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1 g) in methanol (20 ml) and dichloromethane (20 ml) is addedhydroxylamine-O-sulfonic acid (0.28 g) with stirring at roomtemperature, and the mixture is stirred at the same temperature for 1hour. Subsequently, to the reaction solution is added with stirring anaqueous solution of patassium carbonate (0.34 g) in water (1 ml) at roomtemperature, and the mixture is stirred at the same temperature for 2hours. The precipitated crystal is removed by filtration, and thefiltrate is concentrated under reduced pressure. The resulting residueis purified by silica gel column chromatography to give potassium{1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin-5-yl}imino-O-sulfonate(0.4 g) as white powder.

¹ H-NMR (DMSO-d₆) δ; 1.40-1.75 (1H, m), 1.90-2.15 (1H, m), 2.33 (3H, s),2.50-2.80 (2H, m), 3.10-3.50 (1H, m), 4.40-4.65 (1H, m), 6.85-7.60 (10H,m), 7.85 (1H, s), 10.44 (1H, s)

EXAMPLE 926

Using the suitable starting materials, the compounds of above Examples841-843, 868-870, 888 and 889 are obtained in the same manner as inabove Example 380.

EXAMPLE 927

Using the suitable starting materials, the compounds of above Examples876-878 are obtained in the same manner as in above Example 381.

EXAMPLE 928

Using the suitable starting materials, the compounds of above Examples840, 842 and 846 are obtained in the same manner as in above Example384.

EXAMPLE 929

Using the suitable starting materials, the compounds of above Examples788-790, 796-804, 805, 808, 811, 814, 818, 819, 824, 826, 827, 837, 845,848, 850, 852, 855, 856-858, 860, 861, 863-882, 885, 886, 888-893 and895-898 are obtained in the same manner as in above Example 388.

EXAMPLE 930

Using the suitable starting materials, the compound of above Example 848is obtained in the same manner as in above Example 393.

EXAMPLE 931

Using the suitable starting materials, the compounds of above Examples841 and 842 are obtained in the same manner as in above Example 402.

EXAMPLE 932

Using the suitable starting materials, the compounds of above Examples882 and 897 are obtained in the same manner as in above Example 403.

EXAMPLE 933

Using the suitable starting materials, the compound of above Example 809is obtained in the same manner as in above Example 634.

EXAMPLE 934

Using the suitable starting materials, the compounds of above Examples828-838 are obtained in the same manner as in above Example 640.

EXAMPLE 935

Using the suitable starting materials, the compound of above Example 810is obtained in the same manner as in above Example 772.

EXAMPLE 936

Using the suitable starting materials, the compound of above Example 788is obtained in the same manner as in above Example 771.

EXAMPLE 937

Using the suitable starting materials, the compounds of above Examples785, 787, 788-790, 796-805, 806, 807, 808, 811, 814, 818, 819, 845, 848,849, 850, 852, 855, 856-858, 860, 861, 863-882, 885, 886, 888-893 and896-898 are obtained in the same manner as in above Example 390.

EXAMPLE 938

To5-methanesulfonyloxymethyl-1-[4-(2-methylbenzoylamino)benozyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.50 g) is added a 30% solution of methylamine in methanol (50 ml), andthe mixture is heated at 100° C. for 3 hours in a sealed tube. Aftercooling, the reaction solution is evaporated under reduced pressure, andthe resulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol:aqueous ammonia=100:10:1) to give5-methylaminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.07 g).

¹ H-NMR (DMSO-d₆) δ; 1.40-2.18 (4H, m), 2.34 (3H, s), 2.47 (3H, s),2.54-3.50 (4H, m), 4.30-5.08 (1H, m), 6.56-6.82 (1H, m), 6.87-7.48 (10H,m), 7.48-7.75 (2H, m), 10.35 (1H, s)

Using the suitable starting materials, the compounds of above Examples823-825 are obtained in the same manner as in above Example 938.

Using the above suitable starting materials, the compounds of thefollowing Table 6 are obtained in the same manner as in Examples 1 and382.

                  TABLE 6                                                         ______________________________________                                        1 #STR1810##                                                                  ______________________________________                                        Example 939                                                                     Structure                                                                      -                                                                                            2  STR1811##                                                                  3  STR1812##                                                   -                                                                          4  STR1813##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 208-211° C.                                             Form: Free                                                                    Example 940                                                                   Structure                                                                      -                                                                                            2  STR1814##                                                                  3  STR1815##                                                   -                                                                          5  STR1816##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 171.5-172.5° C.                                         Form: Free                                                                    Example 941                                                                   Structure                                                                      -                                                                                            2  STR1817##                                                                  3  STR1818##                                                   -                                                                          6  STR1819##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 151-154° C.                                             Form: Free                                                                    Example 942                                                                   Structure                                                                      -                                                                                            2  STR1820##                                                                  3  STR1821##                                                   -                                                                          7  STR1822##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 167)                                                            Form: Free                                                                    Example 943                                                                   Structure                                                                      -                                                                                            2  STR1823##                                                                  3  STR1824##                                                   -                                                                          8  STR1825##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 180-183° C.                                             Form: Free                                                                    Example 944                                                                   Structure                                                                      -                                                                                            2  STR1826##                                                                  3  STR1827##                                                   -                                                                          9  STR1828##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 109-110° C.                                             Form: Free                                                                    Example 945                                                                   Structure                                                                      -                                                                                            2  STR1829##                                                                  3  STR1830##                                                   -                                                                          0  STR1831##                                                                     - Crystalline form: Colorless oil                                            NMR analysis: 168)                                                            Form: Free                                                                    Example 946                                                                   Structure                                                                      -                                                                                            2  STR1832##                                                                  3  STR1833##                                                   -                                                                          1  STR1834##                                                                     - Crystalline form: Colorless oil                                            NMR analysis: 169)                                                            Form: Free                                                                    Example 947                                                                   Structure                                                                      -                                                                                            2  STR1835##                                                                  3  STR1836##                                                   -                                                                          2  STR1837##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 177-178.5° C.                                           Form: Free                                                                    Example 948                                                                   Structure                                                                      -                                                                                            2  STR1838##                                                                  3  STR1839##                                                   -                                                                          3  STR1840##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 170)                                                            Form: Free                                                                    Example 949                                                                   Structure                                                                      -                                                                                            2  STR1841##                                                                  3  STR1842##                                                   -                                                                          4  STR1843##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 162-165° C.                                             Form: Free                                                                    Example 950                                                                   Structure                                                                      -                                                                                            2  STR1844##                                                                  3  STR1845##                                                   -                                                                          5  STR1846##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 212-215° C.                                             Form: Free                                                                    Example 951                                                                   Structure                                                                      -                                                                                            2  STR1847##                                                                  3  STR1848##                                                   -                                                                          6  STR1849##                                                                     - Crystalline form: Colorless oil                                            NMR analysis 171)                                                             Form: Free                                                                    Example 952                                                                   Structure                                                                      -                                                                                            2  STR1850##                                                                  3  STR1851##                                                   -                                                                          7  STR1852##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 112-114° C.                                             Form: Free                                                                    Example 953                                                                   Structure                                                                      -                                                                                            2  STR1853##                                                                  3  STR1854##                                                   -                                                                          8  STR1855##                                                                     - Crystalline form: Colorless oil                                            NMR analysis: 172)                                                            Form: Free                                                                    Example 954                                                                   Structure                                                                      -                                                                                            2  STR1856##                                                                  3  STR1857##                                                   -                                                                          9  STR1858##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 173)                                                            Form: Free                                                                    Example 955                                                                   Structure                                                                      -                                                                                            2  STR1859##                                                                  3  STR1860##                                                   -                                                                          0  STR1861##                                                                     - Crystalline form: Light yellow amorphous                                   NMR anlaysis: 174)                                                            Form: Free                                                                    Example 956                                                                   Structure                                                                      -                                                                                            2  STR1862##                                                                  3  STR1863##                                                   -                                                                          1  STR1864##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether                                      Melting Point: 189-193° C.                                             Form: Free                                                                    Example 957                                                                   Structure                                                                      -                                                                                            2  STR1865##                                                                  3  STR1866##                                                   -                                                                          2  STR1867##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 175)                                                            Form: Free                                                                    Example 958                                                                   Structure                                                                      -                                                                                            2  STR1868##                                                                  3  STR1869##                                                   -                                                                          4  STR1870##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 234-238° C.                                             Form: Free                                                                    Example 959                                                                   Structure                                                                      -                                                                                            2  STR1871##                                                                  5  STR1872##                                                   -                                                                          6  STR1873##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 183-184.5° C.                                           Form: Free                                                                    Example 960                                                                   Structure                                                                      -                                                                                            2  STR1874##                                                                  5  STR1875##                                                   -                                                                          7  STR1876##                                                                     - Crystalline form: Brown oil                                                NMR analysis: 176)                                                            Form: Free                                                                    Example 961                                                                   Structure                                                                      -                                                                                            2  STR1877##                                                                  8  STR1878##                                                   -                                                                          7  STR1879##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 177)                                                            Form: Free                                                                    Example 962                                                                   Structure                                                                      -                                                                                            2  STR1880##                                                                  9  STR1881##                                                   -                                                                          0  STR1882##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 178)                                                            Form: Free                                                                    Example 963                                                                   Structure                                                                      -                                                                                            2  STR1883##                                                                  1  STR1884##                                                   -                                                                          2  STR1885##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 202.5-204.5° C.                                         Form: Free                                                                    Example 964                                                                   Structure                                                                      -                                                                                            2  STR1886##                                                                  1  STR1887##                                                   -                                                                          3  STR1888##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 199.5-201° C.                                           Form: Free                                                                    Example 965                                                                   Structure                                                                      -                                                                                            2  STR1889##                                                                  4  STR1890##                                                   -                                                                          2  STR1891##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 196.5-197° C.                                           Form: Free                                                                    Example 966                                                                   Structure                                                                      -                                                                                            2  STR1892##                                                                  5  STR1893##                                                   -                                                                          2  STR1894##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 204-205° C.                                             Form: Free                                                                    Example 967                                                                   Structure                                                                      -                                                                                            2  STR1895##                                                                  6  STR1896##                                                   -                                                                          2  STR1897##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 175-177° C.                                             Form: Free                                                                    Example 968                                                                   Structure                                                                      -                                                                                            2  STR1898##                                                                  7  STR1899##                                                   -                                                                          2  STR1900##                                                                     - Crystalline form: Pink amorphous                                           NMR analysis: 179)                                                            Form: Free                                                                    Example 969                                                                   Structure                                                                      -                                                                                            2  STR1901##                                                                  8  STR1902##                                                   -                                                                          2  STR1903##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 186-189° C.                                             Form: Free                                                                    Example 970                                                                   Structure                                                                      -                                                                                            2  STR1904##                                                                  9  STR1905##                                                   -                                                                          0  STR1906##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 211-212° C.                                             Form: Free                                                                    Example 971                                                                   Structure                                                                      -                                                                                            2  STR1907##                                                                  1  STR1908##                                                   -                                                                          2  STR1909##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 180)                                                            Form: Free                                                                    Example 972                                                                   Structure                                                                      -                                                                                            2  STR1910##                                                                  3  STR1911##                                                   -                                                                          2  STR1912##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 206-207° C.                                             Form: Free                                                                    Example 973                                                                   Structure                                                                      -                                                                                            2  STR1913##                                                                  4  STR1914##                                                   -                                                                          5  STR1915##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 181)                                                            Form: Free                                                                    Example 974                                                                   Structure                                                                      -                                                                                            2  STR1916##                                                                  6  STR1917##                                                   -                                                                          7  STR1918##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 152-154° C.                                             Form: Free                                                                    Example 975                                                                   Structure                                                                      -                                                                                            2  STR1919##                                                                  8  STR1920##                                                   -                                                                          9  STR1921##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 182)                                                            Form: Free                                                                    Example 976                                                                   Structure                                                                      -                                                                                            2  STR1922##                                                                  6  STR1923##                                                   -                                                                          0  STR1924##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 204-206° C.                                             Form: Free                                                                    Example 977                                                                   Structure                                                                      -                                                                                            2  STR1925##                                                                  1  STR1926##                                                   -                                                                          2  STR1927##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 162-163° C.                                             Form: Free                                                                  ______________________________________                                            167)   .sup.1 H-NMR(CDCl.sub.3)δ; 1.14-2.83(13H, m), 2.43(3H,                    s), 2.95-5.19(4H, m), 4.12(2H, t, J=6.2Hz),                         6.27-6.83(2H, m), 6.83-7.36(6H, m), 7.36-7.67                                 (4H, m), 7.93-8.11(1H, m), 9.77(1H, brs)                                     168) .sup.1 H-NMR(CDCl.sub.3)δ; 1.11-2.98(11H, m), 2.80(3H,                        s), 3.69(2H, s), 2.98-5.24(2H, m), 6.50-7.71                        (12H, m), 9.37(1H, brs)                                                      169) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10-2.80(14H, m), 2.99(3H,                        s), 3.39-5.20(2H, m), 4.00(2H, s), 6.49-7.67                        (12H, m), 8.51(1H, brs)                                                      170) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10-1.98(3H, m), 1.98-2.82                        (10H, m), 2.82-3.20(2H, m), 3.34-5.15(2H, m),                       6.48-7.68(15H, m), 7.86(1H, brs)                                             171) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10-2.84(10H, m), 2.40(3H,                        s), 2.90-5.20(2H, m), 3.79(2H, d, J=2.7Hz), 4.33                    (1H, br), 6.30-7.68(12H, m), 8.67(1H, brs)                                   172) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10-2.85(14H, m), 2.72(3H,                        s), 2.98-5.20(2H, m), 3.62(2H, s), 6.50-7.75                        (12H, m), 9.18(1H, brs)                                                      173) .sup.1 H-NMR(DMSO-d.sub.6)δ; 1.28-2.62(4H, m), 2.07(3H,                       s), 2.34(6H, s), 3.04-3.57(2H, m), 3.99-4.86(1H,                    m), 6.62-7.88(12H, m), 10.12-10.20(2H, m)                                    174) .sup.1 H-NMR(CDCl.sub.3)δ; 1.39(3H, t, J=7.1Hz), 1.64-                        2.68(4H, m), 2.42(6H, s), 3.04-3.58(2H, m),                         3.98-5.01(1H, m), 4.38(2H, q, J=7.1Hz), 6.57-                                 8.57(13H, m)                                                                 175) .sup.1 H-NMR(DMSO-d.sub.6)δ; 1.67-5.02(7H, m), 3.35(6H,                       s), 6.75-8.17(12H, m), 8.46(1H, s), 10.54(1H, s)                   176) .sup.1 H-NMR(CDCl.sub.3)δ; 1.21(3H, t, J=7.1Hz), 1.95-                        2.30(2H, m), 2.88(2H, t, J=6.2Hz), 3.40-3.65                        (2H, m), 3.70-4.50(2H, m), 3.91(2H, s), 6.66(1H,                              d, J=8.5Hz), 6.70-7.00(3H, m), 7.10-7.50(7H, m),                              7.81(1H, d, J=2.5Hz), 8.44(1H, s)                                            177) .sup.1 H-NMR(CDCl.sub.3)δ: 1.21(3H, t, J=7Hz), 1.30-5.20                      (11H, m), 3.48(2H, q, J=7Hz), 3.90(2H, s), 6.53                     (1H, d, J=8.3Hz), 6.65-7.00(4H, m), 7.00-7.40                                 (6H, m), 7.51(1H, d, J=2.5Hz), 8.40(1H, s)                                   178) .sup.1 H-NMR(CDCl.sub.3)δ; 1.21(3H, t, J=7Hz), 1.20-5.20                      (15H, m), 3.90(2H, s), 6.48(1H, d, J=8.3Hz),                        6.50-7.70(11H, m), 8.39(1H, s)                                               179) .sup.1 H-NMR(CDCl.sub.3)δ; 1.60-2.20(1H, m), 2.10-2.35                        (1H, m), 2.45(3H, s), 2.70-2.95(2H, m), 3.25-3.45                   (1H, m), 4.60-4.85(1H, m), 7.10-7.80(12H, m)                                 180) .sup.1 H-NMR(CDCl.sub.3)δ; 1.65-2.15(4H, m), 2.46(3H, s),                     2.6-5.15(4H, m), 6.75-6.95(1H, m), 7.15-7.55                        (10H, m), 7.61(1H, s), 7.95-8.1(1H, m)                                       181) .sup.1 H-NMR(CDCl.sub.3)δ; 1.60-2.15(3H, m), 2.15-2.90                        (2H, m), 2.90-3.22(6H, m), 4.00-4.50(2H, m), 4.13                   (2H, s), 4.58-5.22(2H, m), 6.53-6.80(1H, m),                                  6.90-7.90(7H, m), 8.48(1H, s)                                                182) .sup.1 H-NMR(CDCl.sub.3)δ; 1.48-2.20(3H, m), 2.20-2.85                        (2H, m), 2.85-3.27(6H, m), 4.05-4.47(2H, m),                        4.47-5.22(2H, m), 6.50-6.76(1H, m), 6.76-6.91                                 (1H, m), 6.91-7.69(9H, m), 7.69-8.13(1H, m), 9.28                             (1H, s), 11.87(1H, brs)                                                    ______________________________________                                    

EXAMPLE 978

5-Dimethylamino-1-(2-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(H) (1.00 g) is dissolved in dichloromethane (30 ml), and thereto isadded triethylamine (0.48 ml) under ice-cooling, and further addeddropwise 2-methylbenzoyl chloride (0.44 ml). The mixture is stirred atroom temperature for 1 hour. The reaction solution is washed with water,and dried over magnesium sulfate. The solvent is distilled off, and theresulting residue is crystallized by adding thereto ethyl acetate. Theprecipitated crystal is recrystallized from dichloromethane/ethylacetate to give5-dimethylamino-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.92 g) as white powder, m.p. 191-192° C.

HPLC retention time: 7.5 minutes

Column; Wakosil II 5C₁₈ (trade mark; Wako Pure Chemical Co., Ltd.)

Solvent; acetonitrile: 50 mN aqueous Na₂ SO₄

solution: acetic acid=27:73:1

Rate; 1.0 ml/min.

[α]_(D) ²² =0° (c=1.0, chloroform); ¹ H-NMR (CDCl₃) δ; 1.15-3.25 (17H,m), 3.35-5.14 (2H, m), 6.62-8.05 (12H, m)

Charts of ¹ H-NMR (CDCl₃) of the starting compound (H) and the compoundobtained in Exmaple 978 are shown in FIG. 1 and FIG. 2, respectively.

EXAMPLE 979

Using5-dimethylamino-1-(2-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(G) (1.00 g),5-dimethylamino-1-(2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.48 g) is obtained in the same manner as in Example 978 except thatmethanol/diethyl ether is used instead of ethyl acetate asrecrystallization solvent, as white powder, m.p. 183-185° C.

HPLC retention time: 8.1 minutes (the conditions of HPLC are same asthose in Example 978)

[α]_(D) ²² =0° (c=1.3, chloroform); ¹ H-NMR (CDCl₃) δ; 1.10-3.20 (17H,m), 3.35-5.15 (2H, m), 6.50-6.80 (1H, m), 6.86-7.62 (10H, m), 7.65-8.09(1H, m)

Charts of ¹ H-NMR (CDCl₃) of the starting compound (G) and the compoundobtained in Exmaple 979 are shown in FIG. 3 and FIG. 4, respectively.

REFERENCE EXAMPLE 18

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

7-Methoxy-5-oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless needles, m.p. 178-178.5° C. (recrystallized from ethylacetate/n-hexane)

7-Methoxy-5-oxo-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 150-151° C. (recrystallized from ethylacetate/n-hexane)

7-Methoxy-5-oxo-1-(3-methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 116-118° C. (recrystallized from ethylacetate/n-hexane)

7-Chloro-5-oxo-1-(3-methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder, m.p. 156-158° C. (recrystallized from diethylether/dichloromethane)

REFERENCE EXAMPLE 19

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

7-Methoxy-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 172.5-173.5° C. (recrystallized from ethylacetate/n-hexane)

7-Methoxy-5-oxo-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 153-155° C. (recrystallized from ethylacetate/n-hexane)

7-Methoxy-5-oxo-1-(3-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless needles, m.p. 170-171° C. (recrystallized from ethylacetate/n-hexane)

7-Chloro-5-oxo-1-(3-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ; 2.05-2.30 (2H, m), 2.85-3.00 (2H, m), 3.70 (3H, s),3.85-4.30 (4H, m), 6.42 (1H, d, J=8.1 Hz), 6.64 (1H, dd, J=1.7 Hz, 8.1Hz), 6.72 (1H, d, J=8.5 Hz), 6.80 (1H, d, J=1.8 Hz), 7.19 (1H, dd, J=2.6Hz, 8.5 Hz), 7.81 (1H, d, J=2.5 Hz)

Using the suitable starting materials, the compounds of the followingTable 7 are obtained in the same manner as in above Examples 1 and 382.

                  TABLE 7                                                         ______________________________________                                        1 #STR1928##                                                                  ______________________________________                                        Example 980                                                                     Structure                                                                   2  STR1929##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR1930##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 183)                                                            Form: Free                                                                    Example 981                                                                   Structure                                                                      -                                                                          2  STR1931##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1932##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 184)                                                            Form: Free                                                                    Example 982                                                                   Structure                                                                      -                                                                          2  STR1933##                                                                     - R.sup.2 : H                                                                 -                                                                          6  STR1934##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 185)                                                            Form: Free                                                                    Example 983                                                                   Structure                                                                      -                                                                          2  STR1935##                                                                     - R.sup.2 : H                                                                 -                                                                          7  STR1936##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 186)                                                            Form: Free                                                                    Example 984                                                                   Structure                                                                      -                                                                          2  STR1937##                                                                     - R.sup.2 : H                                                                 -                                                                          8  STR1938##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 187)                                                            Form: Free                                                                    Example 985                                                                   Structure                                                                      -                                                                          9  STR1939##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          0  STR1940##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 188)                                                            Form: Free                                                                    Example 986                                                                   Structure                                                                      -                                                                          9  STR1941##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          1  STR1942##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 189)                                                            Form: Free                                                                    Example 987                                                                   Structure                                                                      -                                                                          9  STR1943##                                                                     - R.sup.2 : H                                                                 -                                                                          0  STR1944##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      Melting Point: 267-268° C.                                             Form: Free                                                                    Example 988                                                                   Structure                                                                      -                                                                          9  STR1945##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1946##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/water                                      Melting Point: 264-266° C.                                             Form: Free                                                                    Example 989                                                                   Structure                                                                      -                                                                          2  STR1947##                                                                     - R.sup.2 : H                                                                 -                                                                          0  STR1948##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 218-220° C.                                             Form: Free                                                                    Example 990                                                                   Structure                                                                      -                                                                          3  STR1949##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          0  STR1950##                                                                     - Crystalline form: Yellow oil                                               NMR analysis: 190)                                                            Form: Free                                                                    Example 991                                                                   Structure                                                                      -                                                                          3  STR1951##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          1  STR1952##                                                                     - Crystalline form: Yellow oil                                               NMR analysis: 191)                                                            Form: Free                                                                    Example 992                                                                   Structure                                                                      -                                                                          4  STR1953##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          0  STR1954##                                                                     - Crystalline form: Yellow powder                                            Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 174-177° C.                                             Form: Free                                                                    Example 993                                                                   Structure                                                                      -                                                                          5  STR1955##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          0  STR1956##                                                                     - Crystalline form: Yellow amorphous                                         NMR analysis: 192)                                                            Form: Free                                                                    Example 994                                                                   Structure                                                                      -                                                                          6  STR1957##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          0  STR1958##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 193)                                                            Form: Free                                                                    Example 995                                                                   Structure                                                                      -                                                                          4  STR1959##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          1  STR1960##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 163-165° C.                                             Form: Free                                                                    Example 996                                                                   Structure                                                                      -                                                                          5  STR1961##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          1  STR1962##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 194)                                                            Form: Free                                                                    Example 997                                                                   Structure                                                                      -                                                                          6  STR1963##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          1  STR1964##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 195)                                                            Form: Free                                                                  ______________________________________                                         183) .sup.1 HNMR(CDCl.sub.3)δ; 1.10-2.83(11H, m), 2.96-5.21(2H, m),     4.55(2H, s), 6.48-7.72(13H, m), 8.30(1H, brs)                                 184) .sup.1 HNMR(CDCl.sub.3)δ; 1.10-2.85(11H, m), 1.58(3H, d,           J=6.8Hz), 2.23(3H, s), 2.95-5.19(4H, m), 6.38-7.70(12H, m), 8.69(1H, brs)     185) .sup.1 HNMR(CDCl.sub.3)δ; 1.10-2.85(14H, m), 2.26(3H, s),          2.96-5.19(4H, m), 6.36-7.68(12H, m), 8.72(1H, brs)                            186) .sup.1 HNMR(CDCl.sub.3)δ; 1.09-2.72(11H, m), 1.53(3H, d,           J=6.9Hz), 2.24(3H, s), 2.93-5.21(4H, m), 6.30-7.78(12H, m), 8.76(1H, brs)     187) .sup.1 HNMR(CDCl.sub.3)δ; 1.10-2.82(14H, m), 2.96-5.20(4H, m),     6.38-7.70(12H, m), 8.54(1H, brs)                                              188) .sup.1 HNMR(CDCl.sub.3)δ; 1.64-2.28(2H, m), 2.41(3H, s),           2.60-2.90(2H, m), 2.90-3.70(1H, m), 3.76(3H, s), 4.10-5.10(1H, m),            6.60-7.70(10H, m), 8.51(1H, s)                                                189) .sup.1 HNMR(CDCl.sub.3)δ; 1.64-2.43(2H, m), 2.67-2.97(2H, m),      3.00-3.70(1H, m), 3.77(3H, s), 4.20-5.10(1H, m), 6.60-7.75(10H, m),           8.51(1H, s)                                                                   190) .sup.1 HNMR(CDCl.sub.3)δ; 2.00-2.35(2H, m), 2.49(3H, s),           2.89(2H, t, J=6.2Hz), 3.72(3H, s), 3.40-4.80(2H, m), 6.74(2H, d, J=8.5Hz)     6.80-7.00(2H, m), 7.25-7.60(5H, m), 7.80(1H, d, J=2.6Hz), 8.16(1H, s),        8.37(1H, d, J=8.6 Hz)                                                         191) .sup.1 HNMR(CDCl.sub.3)δ; 1.90-2.40(2H, m), 2.90(2H, t,            J=6.2Hz), 3.75(3H, s), 3.40-4.80(2H, m), 6.74(1H, d, J=8.5Hz),                6.80-7.00(2H, m), 7.10-7.50(4H, m), 7.73(1H, dd, J=2.3Hz, 6Hz), 7.80(1H,      d, J=2.5Hz), 8.38(1H, d, J=8.8Hz), 8.65(1H, s)                                192) .sup.1 HNMR(CDCl.sub.3)δ; 1.10-2.10(13H, m), 2.80-5.20(6H, m),     6.56(1H, d, J=8.4Hz), 6.69(1H, d, J=7Hz), 6.85-7.70(7H, m), 8.15(1H, s),      8.31(1H, d, J=8.4Hz)                                                          193) .sup.1 HNMR(CDCl.sub.3)δ; 0.30-0.65(4H, m), 1.20-2.50(7H, m),      2.50(3H, s), 3.10-5.20(2H, m), 3.75(3H, s), 6.60(1H, d, J=8.3Hz),             6.70-7.60(8H, m), 8.14(1H, s), 8.20-8.40(1H, m)                               194) .sup.1 HNMR(CDCl.sub.3)δ; 0.80-2.50(10H, m), 2.90-4.10(6H, m),     6.50-7.80(9H, m), 8.32(1H, d, J=8Hz), 8.62(1H, s)                             195) .sup.1 HNMR(CDCl.sub.3)δ; 0.30-0.65(4H, m), 0.70-2.40(6H, m),      2.60-5.20(6H, m), 6.50-7.80(9H, m), 8.30(1H, d, J=8Hz), 8.62(1H, s)      

REFERENCE EXAMPLE 20

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

7-Methyl-5-oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white needles

¹ H-NMR (CDCl₃) δ; 2.20 (2H, brs), 2.32 (3H, s), 2.88 (2H, t, J=6.3 Hz),3.40-4.79 (2H, m), 6.57 (1H, d, J=8.0 Hz), 7.04 (1H, d, J=7.7 Hz), 7.36(2H, d, J=8.6 Hz), 7.62 (1H, d, J=1.7 Hz), 8.04 (2H, d, J=8.7 Hz)

7-Dimethylamino-5-oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,red brown prisms (recrystallized from dichloromethane/diethyl ether)

¹ H-NMR (CDCl₃) δ; 1.75-2.47 (2H, m), 2.60-3.62, 4.51-4.92 (total 4H,m), 2.93 (6H, s), 6.46 (1H, dd, J=2.2 Hz, 7.0 Hz), 6.52 (1H, d, J=7.0Hz), 7.33 (2H, d, J=7.0 Hz), 8.00 (2H, d, J=7.0 Hz)

7-Bromo-5-oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from dichloromethane/diethyl ether), m.p.177-182° C.

7-Chloro-5-oxo-1-(2-methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from dichloromethane/diethyl ether)

¹ H-NMR (CDCl₃) δ;1.78-2.37 (2H, m), 2.48 (3H, s), 2.88 (2H, t, J=6.1Hz), 3.30-5.12 (2H, m), 6.47-6.82 (1H, m), 6.82-7.09 (1H, m), 7.09-7.27(1H, m), 7.48-8.35 (3H, m)

6-Oxo-1-(2-chloro-4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.7-2.1 (4H, m), 2.85-4.7 (4H, m), 7.12 (1H, d, J=8.4Hz), 7.17-7.51 (4H, m), 7.89 (1H, dd, J=7.8 Hz, 2.1 Hz), 8.11 (1H, d,J=2.2 Hz)

8-Chloro-6-oxo-1-(2-chloro-4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.7-2.15 (4H, m), 2.85-4.8 (4H, m), 7.14 (1H, d,J=8.5 Hz), 7.16 (1H, d, J=8.4 Hz), 7.34 (1H, dd, J=8.3 Hz, 2.5 Hz), 7.85(1H, d, J=2.5 Hz), 7.94 (1H, dd, J=8.4 Hz, 2.2 Hz), 8.13 (1H, d, J=2.1Hz)

8-Methyl-6-oxo-1-(2-chloro-4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.65-2.2 (4H, m), 2.33 (3H, s), 2.7-5.0 (4H, m),7.0-7.25 (3H, m), 7.67 (1H, d, J=2.0 Hz), 7.89 (1H, dd, J=8.4 Hz, 2.2Hz), 8.10 (1H, d, J=2.1 Hz)

8-Methoxy-6-oxo-1-(2-chloro-4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.6-2.05 (4H, m), 2.8-5.2 (4H, m), 3.78 (3H, s), 6.88(1H, dd, J=8.6 Hz, 3.1 Hz), 7.11 (1H, d, J=8.4 Hz), 7.12 (1H, d, J=8.6Hz), 7.38 (1H, d, J=3.0 Hz), 7.90 (1H, dd, J=8.4 Hz, 2.2 Hz), 8.11 (1H,d, J=2.2 Hz)

7-Chloro-5-oxo-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder (recrystallized from diethyl ether/dichloromethane), m.p.125-126.5° C.

REFERENCE EXAMPLE 21

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

7-Methyl-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder

¹ H-NMR (CDCl₃) δ; 2.13 (2H, brs), 2.32 (3H, s), 2.86 (2H, t, J=6.2 Hz),2.89-5.29 (2H, m), 3.86 (2H, brs), 6.41 (2H, m), 6.65 (1H, d, J=8.1 Hz),7.06 (3H, m), 7.65 (1H, d, J=1.7 Hz)

7-Dimethylamino-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow needles (recrystallized from dichloromethane/diethyl ether)

¹ H-NMR (CDCl₃) δ; 1.78-2.49 (2H, m), 2.64-3.78, 4.07-5.02 (total 4H,m), 2.93 (6H, m), 3.96 (2H, m), 6.38 (2H, d, J=8.7 Hz), 6.55 (1H, dd,J=2.7, 8.7 Hz), 6.62 (1H, d, J=8.7 Hz), 6.96-7.18 (3H, m)

7-Bromo-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from methanol/diethyl ether)

¹ H-NMR (CDCl₃) δ; 1.98-2.37 (2H, m), 2.88 (2H, t, J=6.3 Hz), 3.52-4.55(4H, m), 6.28-6.57 (2H, m), 6.57-6.76 (1H, m), 6.92-7.20 (2H, m),7.28-7.42 (1H, m), 7.90-8.09 (1H, m)

7-Chloro-5-oxo-1-(2-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from dichloromethane/diethyl ether), m.p.190-191° C.

6-Oxo-1-(2-chloro-4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.3-2.25 (4H, m), 2.8-4.4 (6H, m), 6.1-6.9 (3H, m),6.95-7.75 (3H, m), 7.8-8.3 (1H, m)

8-Chloro-6-oxo-1-(2-chloro-4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.59-2.2 (4H, m), 2.6-4.4 (6H, m), 6.1-6.9 (3H, m),6.95-7.5 (2H, m), 7.8-8.05 (1H, m)

7-Chloro-5-oxo-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder (recrystallized from diethyl ether/dichloromethane), m.p.188-191.5° C.

Using the suitable starting materials, the compounds of the followingTable 8 are obtained in the same manner as in above Examples 1 and 382.

                  TABLE 8                                                         ______________________________________                                        1  STR1965##                                                                  ______________________________________                                        Example 998                                                                     Structure                                                                   2  STR1966##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR1967##                                                                     - Crystalline form: White powder                                             NMR analysis: 196)                                                            Form: Free                                                                    Example 999                                                                   Structure                                                                      -                                                                          2  STR1968##                                                                     - R.sup.2 : H                                                                 -                                                                          5  STR1969##                                                                     - Crystalline form: White powder                                             NMR analysis: 197)                                                            Form: Free                                                                    Example 1000                                                                  Structure                                                                      -                                                                          6  STR1970##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR1971##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 200-205° C.                                             Form: Free                                                                    Example 1001                                                                  Structure                                                                      -                                                                          7  STR1972##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR1973##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 198)                                                            Form: Free                                                                    Example 1002                                                                  Structure                                                                      -                                                                          8  STR1974##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR1975##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 234-238° C.                                             Form: Free                                                                    Example 1003                                                                  Structure                                                                      -                                                                          9  STR1976##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR1977##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 174-178° C.                                             Form: Free                                                                    Example 1004                                                                  Structure                                                                      -                                                                          2  STR1978##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1979##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 199)                                                            Form: Free                                                                    Example 1005                                                                  Structure                                                                      -                                                                          2  STR1980##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR1981##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 200)                                                            Form: Free                                                                    Example 1006                                                                  Structure                                                                      -                                                                          6  STR1982##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1983##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 201)                                                            Form: Free                                                                    Example 1007                                                                  Structure                                                                      -                                                                          6  STR1984##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR1985##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 202)                                                            Form: Free                                                                    Example 1008                                                                  Structure                                                                      -                                                                          7  STR1986##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          5  STR1987##                                                                     - Crystalline form: Light yellow amorphous                                   MNR analysis: 203)                                                            Form: Free                                                                    Example 1009                                                                  Structure                                                                      -                                                                          7  STR1988##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR1989##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 204)                                                            Form: Free                                                                    Example 1010                                                                  Structure                                                                      -                                                                          0  STR1990##                                                                     - R.sup.2 : H                                                                 -                                                                          1  STR1991##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 205)                                                            Form: Free                                                                    Example 1011                                                                  Structure                                                                      -                                                                          3  STR1992##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          2  STR1993##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 153-155° C.                                             Form: Free                                                                    Example 1012                                                                  Structure                                                                      -                                                                          3  STR1994##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          4  STR1995##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 142-143° C.                                             Form: Free                                                                    Example 1013                                                                  Structure                                                                      -                                                                          5  STR1996##                                                                     - R.sup.2 : H                                                                 -                                                                          2  STR1997##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 176-178° C.                                             Form: Free                                                                    Example 1014                                                                  Structure                                                                      -                                                                          5  STR1998##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR1999##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 186-188° C.                                             Form: Free                                                                    Example 1015                                                                  Structure                                                                      -                                                                          5  STR2000##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          2  STR2001##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 206)                                                            Form: Free                                                                    Example 1016                                                                  Structure                                                                      -                                                                          5  STR2002##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2003##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 207)                                                            Form: Free                                                                    Example 1017                                                                  Structure                                                                      -                                                                          5  STR2004##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          2  STR2005##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 191-191.5° C.                                           Form: Free                                                                    Example 1018                                                                  Structure                                                                      -                                                                          5  STR2006##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          4  STR2007##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 210-212° C.                                             Form: Free                                                                    Example 1019                                                                  Structure                                                                      -                                                                          6  STR2008##                                                                     - R.sup.2 : H                                                                 -                                                                          2  STR2009##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 196-198° C.                                             Form: Free                                                                    Example 1020                                                                  Structure                                                                      -                                                                          6  STR2010##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2011##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 208)                                                            Form: Free                                                                    Example 1021                                                                  Structure                                                                      -                                                                          6  STR2012##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          2  STR2013##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 209)                                                            Form: Free                                                                    Example 1022                                                                  Structure                                                                      -                                                                          6  STR2014##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2015##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 210)                                                            Form: Free                                                                    Example 1023                                                                  Structure                                                                      -                                                                          6  STR2016##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          2  STR2017##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 211)                                                            Form: Free                                                                    Example 1024                                                                  Structure                                                                      -                                                                          6  STR2018##                                                                     - R.sup.2 : 3-OCH.sub.3                                                       -                                                                          4  STR2019##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 212)                                                            Form: Free                                                                    Example 1025                                                                  Structure                                                                      -                                                                          7  STR2020##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          2  STR2021##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 213)                                                            Form: Free                                                                    Example 1026                                                                  Structure                                                                      -                                                                          7  STR2022##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2023##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 214)                                                            Form: Free                                                                    Example 1027                                                                  Structure                                                                      -                                                                          8  STR2024##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2025##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 207-208° C.                                             Form: Free                                                                    Example 1028                                                                  Structure                                                                      -                                                                          8  STR2026##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          2  STR2027##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 201-202° C.                                             Form: Free                                                                    Example 1029                                                                  Structure                                                                      -                                                                          9  STR2028##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2029##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 193-194° C.                                             Form: Free                                                                    Example 1030                                                                  Structure                                                                      -                                                                          8  STR2030##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2031##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 205-208° C.                                             Form: Free                                                                    Example 1031                                                                  Structure                                                                      -                                                                          9  STR2032##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2033##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol                                            Melting Point: 214-216° C.                                             Form: Free                                                                    Example 1032                                                                  Structure                                                                      -                                                                          0  STR2034##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2035##                                                                     - Crystalline form: Yellow needles                                           Recrystallization solvent: Ethanol                                            Melting Point: 223-226° C.                                             Form: Free                                                                    Example 1033                                                                  Structure                                                                      -                                                                          1  STR2036##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2037##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 203-206° C.                                             Form: Free                                                                    Example 1034                                                                  Structure                                                                      -                                                                          2  STR2038##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2039##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/diethyl ether/n-hexane                     Melting Point: 168-171° C.                                             Form: Free                                                                    Example 1035                                                                  Structure                                                                      -                                                                          3  STR2040##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2041##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 206-208° C.                                             Form: Free                                                                    Example 1036                                                                  Structure                                                                      -                                                                          3  STR2042##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2043##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 229-232° C.                                             Form: Free                                                                    Example 1037                                                                  Structure                                                                      -                                                                          4  STR2044##                                                                     - R.sup.2 : H                                                                 -                                                                          2  STR2045##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 220-222° C.                                             Form: Free                                                                    Example 1038                                                                  Structure                                                                      -                                                                          4  STR2046##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2047##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 232-233.5° C.                                           Form: Free                                                                    Example 1039                                                                  Structure                                                                      -                                                                          5  STR2048##                                                                     - R.sup.2 : 2-CH.sub.3                                                        -                                                                          2  STR2049##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 215)                                                            Form: Free                                                                    Example 1040                                                                  Structure                                                                      -                                                                          6  STR2050##                                                                     - R.sup.2 : 2-CH.sub.3                                                        -                                                                          4  STR2051##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 216)                                                            Form: Free                                                                    Example 1041                                                                  Structure                                                                      -                                                                          7  STR2052##                                                                     - R.sup.2 : H                                                                 -                                                                          8  STR2053##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 147-151° C.                                             Form: Free                                                                    Example 1042                                                                  Structure                                                                      -                                                                          7  STR2054##                                                                     - R.sup.2 : H                                                                 -                                                                          9  STR2055##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 127-129° C.                                             Form: Free                                                                    Example 1043                                                                  Structure                                                                      -                                                                          7  STR2056##                                                                     - R.sup.2 : H                                                                 -                                                                          0  STR2057##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 109-112° C.                                             Form: Free                                                                    Example 1044                                                                  Structure                                                                      -                                                                          1  STR2058##                                                                     - R.sup.2 : H                                                                 -                                                                          2  STR2059##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 198-200° C.                                             Form: Free                                                                    Example 1045                                                                  Structure                                                                      -                                                                          2  STR2060##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2061##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 210-211° C.                                             Form: Free                                                                    Example 1046                                                                  Structure                                                                      -                                                                          3  STR2062##                                                                     - R.sup.2 : 2-CH.sub.3                                                        -                                                                          4  STR2063##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 217)                                                            Form: Free                                                                    Example 1047                                                                  Structure                                                                      -                                                                          3  STR2064##                                                                     - R.sup.2 : 2-CH.sub.3                                                        -                                                                          4  STR2065##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 218)                                                            Form: Free                                                                    Example 1048                                                                  Structure                                                                      -                                                                          4  STR2066##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2067##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 219)                                                            Form: Free                                                                    Example 1049                                                                  Structure                                                                      -                                                                          5  STR2068##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2069##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 243-243.5° C.                                           Form: Free                                                                    Example 1050                                                                  Structure                                                                      -                                                                          6  STR2070##                                                                     - R.sup.2 : H                                                                 -                                                                          2  STR2071##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol/petroleum ether                            Melting Point: 207-209° C.                                             Form: Free                                                                    Example 1051                                                                  Structure                                                                      -                                                                          6  STR2072##                                                                     - R.sup.2 : H                                                                 -                                                                          4  STR2073##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/petroleum ether                            Melting Point: 239-241° C.                                             Form: Free                                                                    Example 1052                                                                  Structure                                                                      -                                                                          7  STR2074##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          2  STR2075##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 220)                                                            Form: Free                                                                    Example 1053                                                                  Structure                                                                      -                                                                          8  STR2076##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2077##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 221)                                                            Form: Free                                                                    Example 1054                                                                  Structure                                                                      -                                                                          9  STR2078##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          2  STR2079##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 222)                                                            Form: Free                                                                    Example 1055                                                                  Structure                                                                      -                                                                          9  STR2080##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2081##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 223)                                                            Form: Free                                                                    Example 1056                                                                  Structure                                                                      -                                                                          0  STR2082##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2083##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 169.5-173° C.                                           Form: Free                                                                    Example 1057                                                                  Structure                                                                      -                                                                          0  STR2084##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          2  STR2085##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 224)                                                            Form: Free                                                                    Example 1058                                                                  Structure                                                                      -                                                                          1  STR2086##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2087##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 225)                                                            Example 1059                                                                  Structure                                                                      -                                                                          2  STR2088##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2089##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 226)                                                            Form: Free                                                                    Example 1060                                                                  Structure                                                                      -                                                                          3  STR2090##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2091##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 227)                                                            Form: Free                                                                    Example 1061                                                                  Structure                                                                      -                                                                          4  STR2092##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2093##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 228)                                                            Form: Free                                                                    Example 1062                                                                  Structure                                                                      -                                                                          5  STR2094##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2095##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 229)                                                            Form: Free                                                                    Example 1063                                                                  Structure                                                                      -                                                                          6  STR2096##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2097##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 230)                                                            Form: Free                                                                    Example 1064                                                                  Structure                                                                      -                                                                          7  STR2098##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2099##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 231)                                                            Form: Free                                                                    Example 1065                                                                  Structure                                                                      -                                                                          8  STR2100##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2101##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 232)                                                            Form: Free                                                                    Example 1066                                                                  Structure                                                                      -                                                                          9  STR2102##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2103##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 233)                                                            Form: Free                                                                    Example 1067                                                                  Structure                                                                      -                                                                          0  STR2104##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          4  STR2105##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 234)                                                            Form: Free                                                                    Example 1068                                                                  Structure                                                                      -                                                                          1  STR2106##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          2  STR2107##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 235)                                                            Form: Free                                                                    Example 1069                                                                  Structure                                                                      -                                                                          2  STR2108##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          2  STR2109##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 236)                                                            Form: Free                                                                    Example 1070                                                                  Structure                                                                      -                                                                          3  STR2110##                                                                     - R.sup.2 : 2-Cl                                                              -                                                                          2  STR2111##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 237)                                                            Form: Free                                                                  ______________________________________                                         196) .sup.1 HNMR(CDCl.sub.3)δ; 2.14(2H, brs), 2.33(3H, s), 2.46(3H,     s), 2.85(2H, t, J=6.1Hz), 4.83(2H, brs), 6.64(1H, d, J=8.1Hz), 7.07(1H, d     J=8.0Hz), 7.21-7.48(8H, m), 7.65(1H, m), 7.74(1H, brs)                        197) .sup.1 HNMR(CDCl.sub.3)δ; 2.12(2H, brs), 2.33(3H, s), 2.85(2H,     t, J=6.2Hz), 2.88-5.28(2H, m), 6.63(1H, d, J=8.1Hz), 7.06(1H, dd, J=1.7Hz     8.1Hz), 7.19-7.69(9H, m), 8.26(1H, brs)                                       198) .sup.1 HNMR(CDCl.sub.3)δ; 0.49(4H, m), 1.25-5.13(9H, m),           2.33(3H, s), 2.45(3H, s), 6.53(1H, m), 6.79(1H, m), 7.07-7.42(9H, m),         7.73(1H, m)                                                                   199) .sup.1 HNMR(CDCl.sub.3)δ; 2.04(2H, brs), 2.29(3H, s), 2.82(2H,     t, J=5.9Hz), 2.85-5.29(2H, m), 6.82-7.69(10H, m), 8.31(1H, brs)               200) .sup.1 HNMR(CDCl.sub.3)δ; 2.05(2H, brs), 2.29(3H, s), 2.44(3H,     s), 2.79(2H, t, J=5.5Hz), 2.82-5.28(2H, m), 6.82-8.12(11H, m)                 201) .sup.1 HNMR(CDCl.sub.3)δ; 1.40-4.85(11H, m), 2.51(3H, s),          6.78-7.63(10H, m), 8.64(1H, brs)                                              202) .sup.1 HNMR(CDCl.sub.3)δ; 1.40-4.85(11H, m), 2.45(3H, s),          2.50(3H, s), 6.78-7.55(10H, m), 8.10(1H, brs)                                 203) .sup.1 HNMR(CDCl.sub.3)δ; 0.49(4H, m), 1.25-4.85(9H, m),           2.28(3H, s), 6.77-7.62(10H, m), 8.64(1H, brs)                                 204) .sup.1 HNMR(CDCl.sub.3)δ; 0.48(4H, m), 1.26-4.85(9H, m),           2.29(3H, s), 2.44(3H, s), 6.78-7.58(10H, m), 8.18(1H, brs)                    205) .sup.1 HNMR(CDCl.sub.3)δ; 1.14(6H, d, J=6.3Hz), 1.52-2.20(7H,      m), 2.20-2.60(1H, m), 2.64-3.66(10H, m), 4.00-4.50(4H, m), 4.50-5.23(2H,      m), 6.57-7.90(11H, m), 8.10-8.30(1H, m), 9.97(1H, s)                          206) .sup.1 HNMR(CDCl.sub.3)δ; 1.24-2.08(4H, m), 2.08-2.26(3H, m),      2.26-3.16(4H, m), 3.47-4.03(4H, m), 4.18-4.92(1H, m), 6.40-7.94(10H, m),      8.45-9.03(1H, m)                                                              207) .sup.1 HNMR(CDCl.sub.3)δ; 1.26-2.10(4H, m), 2.10-2.28(3H, m),      2.28-3.20(1H, m), 3.43-4.06(4H, m), 4.20-4.93(1H, m), 6.40-8.00(10H, m),      8.78-9.30(1H, m)                                                              208) .sup.1 HNMR(CDCl.sub.3)δ; 1.10-1.98(4H, m), 1.98-3.10(7H, m),      3.30-3.90(4H, m), 3.90-5.10(1H, m), 6.45-8.25(12H, m)                         209) .sup.1 HNMR(CDCl.sub.3)δ; 1.06-1.94(4H, m), 1.94-3.19(10H, m),     3.19-3.90(4H, m), 3.90-5.10(1H, m), 6.44-8.60(11H, m)                         210) .sup.1 HNMR(CDCl.sub.3)δ; 1.06-1.97(4H, m), 1.97-3.20(7H, m),      3.20-3.92(4H, m), 3.92-5.10(1H, m), 6.44-8.55(11H, m)                         211) .sup.1 HNMR(CDCl.sub.3)δ; 1.07-1.98(4H, m), 1.98-3.10(10H, m),     3.37-5.20(8H, m), 6.44-6.86(3H, m), 6.97-7.60(6H, m), 8.13(1H, s),            8.19-8.38(1H, m)                                                              212) .sup.1 HNMR(CDCl.sub.3)δ; 1.08-1.99(4H, m), 1.99-3.13(7H, m),      3.33-5.14(8H, m), 6.40-6.90(3H, m), 6.95-7.56(5H, m), 7.63-7.87(1H, m),       8.17-8.37(1H, m), 8.60(1H, s)                                                 213) .sup.1 HNMR(CDCl.sub.3)δ; 0.30-0.64(4H, m), 0.70-3.42(9H, m),      3.42-5.10(5H, m), 6.40-8.70(11H, m)                                           214) .sup.1 HNMR(CDCl.sub.3)δ; 0.30-0.76(4H, m), 0.80-3.43(6H, m),      3.50-5.00(5H, m), 6.40-9.04(11H, m)                                           215) .sup.1 HNMR(CDCl.sub.3)δ; 1.25-3.25(14H, m), 3.55-5.06(2H, m),     6.43-7.00(2H, m), 7.00-7.71(8H, m), 7.91-8.45(1H, m)                          216) .sup.1 HNMR(CDCl.sub.3)δ; 1.11-3.20(17H, m), 3.28-5.12(2H, m),     6.41-7.01(2H, m), 7.02-7.63(8H, m), 7.76-8.21(1H, m)                          217) .sup.1 HNMR(CDCl.sub.3)δ; 1.92-2.29(2H, m), 2.36(3H, s),           2.45(3H, s), 2.84(2H, t, J=6.3Hz), 3.32-4.64(2H, m), 6.40-8.10(11H, m)        218) .sup.1 HNMR(CDCl.sub.3)δ; 1.92-2.25(2H, m), 2.34(3H, s),           2.83(2H, t, J=6.3Hz), 3.21-4.52(2H, m), 6.39-7.97(10H, m), 8.43(1H, brs)      219) .sup.1 HNMR(CDCl.sub.3)δ; 1.7-2.15(4H, m), 2.5-5.2(4H, m),         6.75-6.9(1H, m), 7.27-7.6(9H, m), 7.65-7.85(1H, m), 7.9-8.15(2H, m)           220) .sup.1 HNMR(CDCl.sub.3)δ; 1.65-2.1(4H, m), 2.44(3H, s),            2.8-4.5(4H, m), 6.75-8.0(12H, m)                                              221) .sup.1 HNMR(CDCl.sub.3)δ; 1.65-2.3(4H, m), 2.7-4.8(4H, m),         6.75-8.4(12H, m)                                                              222) .sup.1 HNMR(CDCl.sub.3)δ; 1.45-2.15(4H, m), 2.45-2.55(3H, m),      2.85-4.6(4H, m), 6.8-8.25(11H, m)                                             223) .sup.1 HNMR(CDCl.sub.3)δ; 1.5-2.2(4H, m), 2.8-4.7(4H, m),          6.8-8.4(11H, m)                                                               224) .sup.1 HNMR(CDCl.sub.3)δ; 1.75-2.25(2H, m), 2.30-2.70(3H, m),      2.70-2.95(2H, m), 3.20-5.10(2H, m), 6.70-8.40(11H, m)                         225) .sup.1 HNMR(CDCl.sub.3)δ; 1.20-2.60(8H, m), 2.60-5.10(3H, m),      6.80-7.90(10H, m), 8.20-8.60(1H, m)                                           226) .sup.1 HNMR(CDCl.sub.3)δ; 1.20-2.60(10H, m), 2.60-5.10(3H, m),     6.80-8.15(11H, m)                                                             227) .sup.1 HNMR(CDCl.sub.3)δ; 0.30-0.70(4H, m), 1.20-2.45(6H, m),      2.60-5.10(3H, m), 6.80-7.95(10H, m), 8.15-8.50(1H, m)                         228) .sup.1 HNMR(CDCl.sub.3)δ; 1.20-2.40(5H, m), 2.60-5.35(7H, m),      5.80-6.15(1H, m), 6.75-7.95(10H, m), 8.20-8.70(1H, m)                         229) .sup.1 HNMR(CDCl.sub.3)δ; 1.20-2.55(7H, m), 2.60-5.35(7H, m),      5.85-6.05(1H, m), 6.70-7.10(2H, m), 7.10-7.90(8H, m), 8.15-8.60(1H, m)        230) .sup.1 HNMR(CDCl.sub.3)δ; 1.00-1.20(6H, m), 1.00-2.40(5H, m),      2.60-5.10(4H, m), 6.80-8.00(10H, m), 8.15-8,65(1H, m)                         231) .sup.1 HNMR(CDCl.sub.3)δ; 0.80-2.50(13H, m), 2.60-5.10(4H, m),     6.70-8.85(10H, m), 8.25-8.60(1H, m)                                           232) .sup.1 HNMR(CDCl.sub.3)δ; 1.30-2.60(11H, m), 2.60-5.10(3H, m),     6.80-8.15(11H, m)                                                             233) .sup.1 HNMR(CDCl.sub.3)δ; 1.10-2.50(13H, m), 2.50-5.10(3H, m),     6.75-8.40(11H, m)                                                             234) .sup.1 HNMR(CDCl.sub.3)δ; 0.30-0.65(4H, m), 1.20-2.30(6H, m),      2.35-2.55(3H, m), 2.60-5.10(3H, m), 6.75-8.35(11H, m)                         235) .sup.1 HNMR(CDCl.sub.3)δ; 1.20-2.60(8H, m), 2.60-5.40(7H, m),      5.80-6.15(1H, m), 6.80-8.20(11H, m)                                           236) .sup.1 HNMR(CDCl.sub.3)δ; 1.25-2.60(10H, m), 2.60-5.40(7H, m),     5.75-6.10(1H, m), 6.75-7.10(2H, m), 7.10-8.40(9H, m)                          237) .sup.1 HNMR(CDCl.sub.3)δ; 0.95-1.20(6H, m), 0.95-2.25(5H, m),      2.40-2.60(3H, m), 2.60-5.10(4H, m), 6.75-7.05(2H, m), 7.10-8.30(9H, m)   

REFERENCE EXAMPLE 22

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

8-Chloro-6-oxo-1-(4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,yellow prisms

¹ H-NMR (DMSO-d₆) δ; 1.3-2.2 (4H, m), 2.6-5.0 (4H, m), 7.05-8.5 (7H, m)

5-Oxo-7-methyl-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.71-2.32 (2H, m), 2.29 (3H, s), 2.86 (2H, t, J=6.3Hz), 3.10-5.30 (2H, m), 6.84-8.38 (6H, m)

5-Oxo-7-methyl-1-(3-methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 2.17 (2H, brs), 2.34 (3H, s), 2.84 (2H, t, J=6.0 Hz),3.10-5.29 (2H, m), 3.77 (3H, s), 6.67 (1H, d, J=7.9 Hz), 6.85 (2H, m),7.10 (1H, d, J=8.0 Hz), 7.57-7.65 (2H, m)

5-Oxo-7-dimethylamino-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder

¹ H-NMR (CDCl₃) δ; 1.66-2.38 (2H, m), 2.65-2.88 (2H, m), 2.92 (6H, s),3.08-3.64, 4.58-5.01 (total 2H, m), 6.49 (1H, dd, J=3.1, 8.7 Hz), 6.82(1H, d, J=8.7 Hz), 6.90 (1H, d, J=3.1 Hz), 7.02-7.37 (1H, m), 7.94 (1H,dd, J=1.9, 8.4 Hz), 8.08 (1H, d, J=1.9 Hz)

REFERENCE EXAMPLE 23

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

8-Chloro-6-oxo-1-(4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.7-2.2 (4H, m), 2.3-4.8 (6H, m), 6.4-6.6 (2H, m),6.74 (1H, d, J=8.5 Hz), 7.1-7.4 (3H, m), 7.99 (1H, d, J=2.6 Hz)

8-Methyl-6-oxo-(2-chloro-4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,colorless amorphous

¹ H-NMR (CDCl₃) δ; 1.4-2.1 (4H, m), 2.15-2.6 (3H, m), 2.7-4.4 (6H, m),6.15-6.35 (1H, m), 6.51 (1H, s), 6.6-6.85 (1H, m), 6.9-7.25 (2H, m),7.72 (1H, s)

8-Methoxy-6-oxo-(2-chloro-4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.4-2.2 (4H, m), 2.7-5.0 (9H, m), 6.25 (1H, dd, J=8.3Hz, 2.2 Hz), 6.51 (1H, d, J=2.2 Hz), 6.66 (1H, d, J=8.3 Hz), 6.88 (1H,dd, J=8.6 Hz, 3.0 Hz), 7.23 (1H, d, J=8.6 Hz), 7.43 (1H, d, J=3.0 Hz)

5-Oxo-7-chloro-1-(2-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless particles (recrystallized from methanol/diethyl ether), m.p.206-208° C.

5-Oxo-7-methyl-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 2.09 (2H, brs), 2.29 (3H, s), 3.10-5.00 (2H, m), 3.78(2H, brs), 6.34-7.54 (6H, m)

5-Oxo-7-methyl-1-(3-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 2.12 (2H, brs), 2.32 (3H, s), 2.85 (2H, t, J=5.9 Hz),3.30-5.00 (2H, m), 3.65 (3H, s), 3.98 (2H, brs), 6.40 (1H, d, J=8.1 Hz),6.64-6.76 (3H, m), 7.06 (1H, dd, J=1.6, 8.1 Hz), 7.63 (1H, d, J=2.0 Hz)

5-Oxo-7-dimethylamino-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.60-2.32 (2H, m), 2.67-5.13 (4H, m), 2.92 (6H, s),3.75 (2H, s), 6.31 (1H, dd, J=2.1, 8.3 Hz), 6.46 (1H, d, J=2.1 Hz), 6.48(1H, dd, J=3.1, 8.7 Hz), 6.66-6.89 (2H, m), 6.95 (1H, d, J=3.1 Hz)

Using the stuitable starting materials, the compounds of the followingTable 9 are obtained in the same manner as in above Examples 1 and 382.

                  TABLE 9                                                         ______________________________________                                        1 #STR2112##                                                                  ______________________________________                                        Example 1071                                                                    Structure                                                                   2  STR2113##                                                                     -                                                                          3  STR2114##                                                                     -                                                                          4  STR2115##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 227-230° C.                                             Form: Free                                                                    Example 1072                                                                  Structure                                                                      -                                                                          2  STR2116##                                                                     -                                                                          5  STR2117##                                                                     -                                                                          4  STR2118##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/petroleum ether                            Melting Point: 216-218° C.                                             Form: Free                                                                    Example 1073                                                                  Structure                                                                      -                                                                          2  STR2119##                                                                     -                                                                          5  STR2120##                                                                     -                                                                          6  STR2121##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 227-228° C.                                             Form: Free                                                                    Example 1074                                                                  Structure                                                                      -                                                                          2  STR2122##                                                                     -                                                                          7  STR2123##                                                                     -                                                                          6  STR2124##                                                                     - Crystalline form: White powder                                             NMR analysis: 238)                                                            Form: Free                                                                    Example 1075                                                                  Structure                                                                      -                                                                          2  STR2125##                                                                     -                                                                          7  STR2126##                                                                     -                                                                          4  STR2127##                                                                     - Crystalline form: White powder                                             NMR analysis: 239)                                                            Form: Free                                                                    Example 1076                                                                  Structure                                                                      -                                                                          2  STR2128##                                                                     -                                                                          8  STR2129##                                                                     -                                                                          6  STR2130##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 240)                                                            Form: Free                                                                    Example 1077                                                                  Structure                                                                      -                                                                          2  STR2131##                                                                     -                                                                          8  STR2132##                                                                     -                                                                          4  STR2133##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 241)                                                            Form: Free                                                                    Example 1078                                                                  Structure                                                                      -                                                                          2  STR2134##                                                                     -                                                                          2  STR2135##                                                                     -                                                                          6  STR2136##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 242)                                                            Form: Free                                                                    Example 1079                                                                  Structure                                                                      -                                                                          2  STR2137##                                                                     -                                                                          2  STR2138##                                                                     -                                                                          4  STR2139##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 243)                                                            Form: Free                                                                    Example 1080                                                                  Structure                                                                      -                                                                          2  STR2140##                                                                     -                                                                          9  STR2141##                                                                     -                                                                          6  STR2142##                                                                     - Crystalline form: Light yellow powder                                      Recrystallization solvent: Ethyl acetate/diethyl ether                        Melting Point: 179-181° C.                                             Form: Free                                                                    Example 1081                                                                  Structure                                                                      -                                                                          2  STR2143##                                                                     -                                                                          9  STR2144##                                                                     -                                                                          4  STR2145##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/diethyl ether                        Melting Point: 213-216° C.                                             Form: Free                                                                    Example 1082                                                                  Structure                                                                      -                                                                          2  STR2146##                                                                     -                                                                          3  STR2147##                                                                     -                                                                          6  STR2148##                                                                     - Crystalline form: Light yellow powder                                      Recrystallization solvent: Ethyl acetate/diethyl ether                        Melting Point: 185-187° C.                                             Form: Free                                                                    Example 1083                                                                  Structure                                                                      -                                                                          2  STR2149##                                                                     -                                                                          5  STR2150##                                                                     -                                                                          6  STR2151##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol                                            Melting Point: 249-251° C.                                             Form: Free                                                                    Example 1084                                                                  Structure                                                                      -                                                                          2  STR2152##                                                                     -                                                                          5  STR2153##                                                                     -                                                                          4  STR2154##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol                                            Melting Point: 239-241° C.                                             Form: Free                                                                    Example 1085                                                                  Structure                                                                      -                                                                          2  STR2155##                                                                     -                                                                          3  STR2156##                                                                     -                                                                          4  STR2157##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/diethyl ether                        Melting Point: 208-210° C.                                             Form: Free                                                                    Example 1086                                                                  Structure                                                                      -                                                                          2  STR2158##                                                                     -                                                                          0  STR2159##                                                                     -                                                                          6  STR2160##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 178-108.5° C.                                           Form: Free                                                                    Example 1087                                                                  Structure                                                                      -                                                                          2  STR2161##                                                                     -                                                                          1  STR2162##                                                                     -                                                                          4  STR2163##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 244)                                                            Form: Free                                                                    Example 1088                                                                  Structure                                                                      -                                                                          2  STR2164##                                                                     -                                                                          2  STR2165##                                                                     -                                                                          4  STR2166##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 245)                                                            Form: Free                                                                    Example 1089                                                                  Structure                                                                      -                                                                          2  STR2167##                                                                     -                                                                          3  STR2168##                                                                     -                                                                          4  STR2169##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             NMR analysis: 246)                                                            Form: Free                                                                    Example 1090                                                                  Structure                                                                      -                                                                          2  STR2170##                                                                     -                                                                          3  STR2171##                                                                     -                                                                          6  STR2172##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 247)                                                            Form: Free                                                                    Example 1091                                                                  Structure                                                                      -                                                                          2  STR2173##                                                                     -                                                                          3  STR2174##                                                                     -                                                                          4  STR2175##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 248)                                                            Form: Free                                                                    Example 1092                                                                  Structure                                                                      -                                                                          2  STR2176##                                                                     -                                                                          5  STR2177##                                                                     -                                                                          6  STR2178##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 249)                                                            Form: Free                                                                    Example 1093                                                                  Structure                                                                      -                                                                          2  STR2179##                                                                     -                                                                          2  STR2180##                                                                     -                                                                          6  STR2181##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 205-206° C.                                             Form: Free                                                                    Example 1094                                                                  Structure                                                                      -                                                                          2  STR2182##                                                                     -                                                                          0  STR2183##                                                                     -                                                                          6  STR2184##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 250)                                                            Form: Free                                                                    Example 1095                                                                  Structure                                                                      -                                                                          2  STR2185##                                                                     -                                                                          1  STR2186##                                                                     -                                                                          4  STR2187##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 172.5-174° C.                                           Form: Free                                                                    Example 1096                                                                  Structure                                                                      -                                                                          2  STR2188##                                                                     -                                                                          2  STR2189##                                                                     -                                                                          4  STR2190##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 215-216.5° C.                                           Form: Free                                                                    Example 1097                                                                  Structure                                                                      -                                                                          2  STR2191##                                                                     -                                                                          6  STR2192##                                                                     -                                                                          4  STR2193##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 133-136° C.                                             Form: Free                                                                    Example 1098                                                                  Structure                                                                      -                                                                          2  STR2194##                                                                     -                                                                          4  STR2195##                                                                     -                                                                          6  STR2196##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 251)                                                            Form: Free                                                                    Example 1099                                                                  Structure                                                                      -                                                                          2  STR2197##                                                                     -                                                                          4  STR2198##                                                                     -                                                                          4  STR2199##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 179-180° C.                                             Form: Free                                                                    Example 1100                                                                  Structure                                                                      -                                                                          2  STR2200##                                                                     -                                                                          5  STR2201##                                                                     -                                                                          6  STR2202##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/n-hexane                                  Melting Point: 167.5-169.5° C.                                         Form: Free                                                                    Example 1101                                                                  Structure                                                                      -                                                                          2  STR2203##                                                                     -                                                                          5  STR2204##                                                                     -                                                                          4  STR2205##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 176-178° C.                                             Form: Free                                                                    Example 1102                                                                  Structure                                                                      -                                                                          2  STR2206##                                                                     -                                                                          7  STR2207##                                                                     -                                                                          6  STR2208##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 252)                                                            Form: Free                                                                    Example 1103                                                                  Structure                                                                      -                                                                          2  STR2209##                                                                     -                                                                          0  STR2210##                                                                     -                                                                          4  STR2211##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 185-188° C.                                             Form: Free                                                                    Example 1104                                                                  Structure                                                                      -                                                                          2  STR2212##                                                                     -                                                                          8  STR2213##                                                                     -                                                                          6  STR2214##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 180-181.5° C.                                           Form: Free                                                                    Example 1105                                                                  Structure                                                                      -                                                                          2  STR2215##                                                                     -                                                                          9  STR2216##                                                                     -                                                                          6  STR2217##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 181-184° C.                                             Form: Free                                                                    Example 1106                                                                  Structure                                                                      -                                                                          2  STR2218##                                                                     -                                                                          8  STR2219##                                                                     -                                                                          4  STR2220##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 186.5-187° C.                                           Form: Free                                                                    Example 1107                                                                  Structure                                                                      -                                                                          2  STR2221##                                                                     -                                                                          9  STR2222##                                                                     -                                                                          4  STR2223##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 183-184° C.                                             Form: Free                                                                    Example 1108                                                                  Structure                                                                      -                                                                          2  STR2224##                                                                     -                                                                          6  STR2225##                                                                     -                                                                          6  STR2226##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 151-153° C.                                             Form: Free                                                                    Example 1109                                                                  Structure                                                                      -                                                                          2  STR2227##                                                                     -                                                                          0  STR2228##                                                                     -                                                                          1  STR2229##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 253)                                                            Form: Free                                                                    Example 1110                                                                  Structure                                                                      -                                                                          2  STR2230##                                                                     -                                                                          2  STR2231##                                                                     -                                                                          3  STR2232##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 254)                                                            Form: Free                                                                    Example 1111                                                                  Structure                                                                      -                                                                          2  STR2233##                                                                     -                                                                          4  STR2234##                                                                     -                                                                          3  STR2235##                                                                     - Crystalline form: White needles                                            Recrystallization solvent: Ethanol/n-hexane                                   Melting Point: 191-195° C.                                             Form: Free                                                                    Example 1112                                                                  Structure                                                                      -                                                                          2  STR2236##                                                                     -                                                                          5  STR2237##                                                                     -                                                                          3  STR2238##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/n-hexane                             Melting Point: 227-230° C.                                             Form: Free                                                                    Example 1113                                                                  Structure                                                                      -                                                                          2  STR2239##                                                                     -                                                                          6  STR2240##                                                                     -                                                                          1  STR2241##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 289)                                                            Form: Free                                                                    Example 1114                                                                  Structure                                                                      -                                                                          2  STR2242##                                                                     -                                                                          6  STR2243##                                                                     -                                                                          3  STR2244##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 255)                                                            Example 1115                                                                  Structure                                                                      -                                                                          2  STR2245##                                                                     -                                                                          7  STR2246##                                                                     -                                                                          1  STR2247##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/n-hexane                             Melting Point: 172-174° C.                                             Form: Free                                                                    Example 1116                                                                  Structure                                                                      -                                                                          2  STR2248##                                                                     -                                                                          8  STR2249##                                                                     -                                                                          1  STR2250##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 305)                                                            Form: Free                                                                    Example 1117                                                                  Structure                                                                      -                                                                          2  STR2251##                                                                     -                                                                          6  STR2252##                                                                     -                                                                          1  STR2253##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 290)                                                            Form: Free                                                                    Example 1118                                                                  Structure                                                                      -                                                                          2  STR2254##                                                                     -                                                                          7  STR2255##                                                                     -                                                                          1  STR2256##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 291)                                                            Form: Free                                                                    Example 1119                                                                  Structure                                                                      -                                                                          2  STR2257##                                                                     -                                                                          9  STR2258##                                                                     -                                                                          6  STR2259##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 264)                                                            Form: Free                                                                    Example 1120                                                                  Structure                                                                      -                                                                          2  STR2260##                                                                     -                                                                          9  STR2261##                                                                     -                                                                          4  STR2262##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 265)                                                            Form: Free                                                                    Example 1121                                                                  Structure                                                                      -                                                                          2  STR2263##                                                                     -                                                                          0  STR2264##                                                                     -                                                                          6  STR2265##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 266)                                                            Form: Free                                                                    Example 1122                                                                  Structure                                                                      -                                                                          2  STR2266##                                                                     -                                                                          0  STR2267##                                                                     -                                                                          4  STR2268##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 267)                                                            Form: Free                                                                    Example 1123                                                                  Structure                                                                      -                                                                          2  STR2269##                                                                     -                                                                          1  STR2270##                                                                     -                                                                          6  STR2271##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 268)                                                            Form: Free                                                                    Example 1124                                                                  Structure                                                                      -                                                                          2  STR2272##                                                                     -                                                                          1  STR2273##                                                                     -                                                                          4  STR2274##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 269)                                                            Form: Free                                                                    Example 1125                                                                  Structure                                                                      -                                                                          2  STR2275##                                                                     -                                                                          2  STR2276##                                                                     -                                                                          6  STR2277##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 270)                                                            Form: Free                                                                    Example 1126                                                                  Structure                                                                      -                                                                          2  STR2278##                                                                     -                                                                          2  STR2279##                                                                     -                                                                          4  STR2280##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 271)                                                            Form: Free                                                                    Example 1127                                                                  Structure                                                                      -                                                                          2  STR2281##                                                                     -                                                                          8  STR2282##                                                                     -                                                                          6  STR2283##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 272)                                                            Form: Free                                                                    Example 1128                                                                  Structure                                                                      -                                                                          2  STR2284##                                                                     -                                                                          8  STR2285##                                                                     -                                                                          4  STR2286##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 273)                                                            Form: Free                                                                    Example 1129                                                                  Structure                                                                      -                                                                          2  STR2287##                                                                     -                                                                          3  STR2288##                                                                     -                                                                          6  STR2289##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 274)                                                            Form: Free                                                                    Example 1130                                                                  Structure                                                                      -                                                                          2  STR2290##                                                                     -                                                                          3  STR2291##                                                                     -                                                                          4  STR2292##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 275)                                                            Form: Free                                                                    Example 1131                                                                  Structure                                                                      -                                                                          2  STR2293##                                                                     -                                                                          9  STR2294##                                                                     -                                                                          6  STR2295##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 276)                                                            Form: Free                                                                    Example 1132                                                                  Structure                                                                      -                                                                          2  STR2296##                                                                     -                                                                          9  STR2297##                                                                     -                                                                          4  STR2298##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 277)                                                            Form: Free                                                                    Example 1133                                                                  Structure                                                                      -                                                                          2  STR2299##                                                                     -                                                                          4  STR2300##                                                                     -                                                                          6  STR2301##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 278)                                                            Form: Free                                                                    Example 1134                                                                  Structure                                                                      -                                                                          2  STR2302##                                                                     -                                                                          4  STR2303##                                                                     -                                                                          4  STR2304##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 279)                                                            Form: Free                                                                    Example 1135                                                                  Structure                                                                      -                                                                          2  STR2305##                                                                     -                                                                          0  STR2306##                                                                     -                                                                          6  STR2307##                                                                     - NMR analysis: 280)                                                         Form: Free                                                                    Example 1136                                                                  Structure                                                                      -                                                                          2  STR2308##                                                                     -                                                                          0  STR2309##                                                                     -                                                                          4  STR2310##                                                                     - NMR analysis: 281)                                                         Form: Free                                                                    Example 1137                                                                  Structure                                                                      -                                                                          2  STR2311##                                                                     -                                                                          1  STR2312##                                                                     -                                                                          6  STR2313##                                                                     - NMR analysis: 282)                                                         Form: Free                                                                    Example 1138                                                                  Structure                                                                      -                                                                          2  STR2314##                                                                     -                                                                          1  STR2315##                                                                     -                                                                          4  STR2316##                                                                     - NMR analysis: 283)                                                         Form: Free                                                                    Example 1139                                                                  Structure                                                                      -                                                                          2  STR2317##                                                                     -                                                                          2  STR2318##                                                                     -                                                                          6  STR2319##                                                                     - NMR analysis: 306)                                                         Form: Free                                                                    Example 1140                                                                  Structure                                                                      -                                                                          2  STR2320##                                                                     -                                                                          3  STR2321##                                                                     -                                                                          6  STR2322##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 284)                                                            Form: Free                                                                    Example 1141                                                                  Structure                                                                      -                                                                          2  STR2323##                                                                     -                                                                          4  STR2324##                                                                     -                                                                          3  STR2325##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 285)                                                            Form: Free                                                                    Example 1142                                                                  Structure                                                                      -                                                                          2  STR2326##                                                                     -                                                                          4  STR2327##                                                                     -                                                                          1  STR2328##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 286)                                                            Form: Free                                                                    Example 1143                                                                  Structure                                                                      -                                                                          2  STR2329##                                                                     -                                                                          6  STR2330##                                                                     -                                                                          1  STR2331##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 287)                                                            Form: Free                                                                    Example 1144                                                                  Structure                                                                      -                                                                          2  STR2332##                                                                     -                                                                          7  STR2333##                                                                     -                                                                          1  STR2334##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 203-207° C.                                             Form: Free                                                                    Example 1145                                                                  Structure                                                                      -                                                                          2  STR2335##                                                                     -                                                                          7  STR2336##                                                                     -                                                                          3  STR2337##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 199-203° C.                                             Form: Free                                                                    Example 1146                                                                  Structure                                                                      -                                                                          2  STR2338##                                                                     -                                                                          8  STR2339##                                                                     -                                                                          1  STR2340##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 210-212° C.                                             Form: Free                                                                    Example 1147                                                                  Structure                                                                      -                                                                          2  STR2341##                                                                     -                                                                          8  STR2342##                                                                     -                                                                          3  STR2343##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 211-214° C.                                             Form: Free                                                                    Example 1148                                                                  Structure                                                                      -                                                                          2  STR2344##                                                                     -                                                                          9  STR2345##                                                                     -                                                                          1  STR2346##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 186-189° C.                                             Form: Free                                                                    Example 1149                                                                  Structure                                                                      -                                                                          2  STR2347##                                                                     -                                                                          9  STR2348##                                                                     -                                                                          3  STR2349##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 288)                                                            Form: Free                                                                    Example 1150                                                                  Structure                                                                      -                                                                          2  STR2350##                                                                     -                                                                          0  STR2351##                                                                     -                                                                          1  STR2352##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 292)                                                            Form: Free                                                                    Example 1151                                                                  Structure                                                                      -                                                                          2  STR2353##                                                                     -                                                                          0  STR2354##                                                                     -                                                                          3  STR2355##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 293)                                                            Form: Free                                                                    Example 1152                                                                  Structure                                                                      -                                                                          2  STR2356##                                                                     -                                                                          1  STR2357##                                                                     -                                                                          1  STR2358##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 144-145° C.                                             Form: Free                                                                    Example 1153                                                                  Structure                                                                      -                                                                          2  STR2359##                                                                     -                                                                          1  STR2360##                                                                     -                                                                          3  STR2361##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 149-150° C.                                             Form: Free                                                                    Example 1154                                                                  Structure                                                                      -                                                                          2  STR2362##                                                                     -                                                                          2  STR2363##                                                                     -                                                                          1  STR2364##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 294)                                                            Form: Free                                                                    Example 1155                                                                  Structure                                                                      -                                                                          2  STR2365##                                                                     -                                                                          2  STR2366##                                                                     -                                                                          3  STR2367##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 295)                                                            Form: Free                                                                    Example 1156                                                                  Structure                                                                      -                                                                          2  STR2368##                                                                     -                                                                          3  STR2369##                                                                     -                                                                          1  STR2370##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 301)                                                            Form: Free                                                                    Example 1157                                                                  Structure                                                                      -                                                                          2  STR2371##                                                                     -                                                                          3  STR2372##                                                                     -                                                                          3  STR2373##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 302)                                                            Form: Free                                                                    Example 1158                                                                  Structure                                                                      -                                                                          2  STR2374##                                                                     -                                                                          4  STR2375##                                                                     -                                                                          1  STR2376##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 303)                                                            Form: Free                                                                    Example 1159                                                                  Structure                                                                      -                                                                          2  STR2377##                                                                     -                                                                          4  STR2378##                                                                     -                                                                          3  STR2379##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 304)                                                            Form: Free                                                                    Example 1160                                                                  Structure                                                                      -                                                                          2  STR2380##                                                                     -                                                                          5  STR2381##                                                                     -                                                                          6  STR2382##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/diisopropyl ether                    Melting Point: 191-193° C.                                             Form: Free                                                                    Example 1161                                                                  Structure                                                                      -                                                                          2  STR2383##                                                                     -                                                                          5  STR2384##                                                                     -                                                                          4  STR2385##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/diisopropyl ether                    Melting Point: 221-223° C.                                             Form: Free                                                                    Example 1162                                                                  Structure                                                                      -                                                                          2  STR2386##                                                                     -                                                                          5  STR2387##                                                                     -                                                                          6  STR2388##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 159-161° C.                                             Form: Free                                                                    Example 1163                                                                  Structure                                                                      -                                                                          2  STR2389##                                                                     -                                                                          5  STR2390##                                                                     -                                                                          4  STR2391##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 174-175° C.                                             Form: Free                                                                    Example 1164                                                                  Structure                                                                      -                                                                          2  STR2392##                                                                     -                                                                          6  STR2393##                                                                     -                                                                          6  STR2394##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 256)                                                            Form: Free                                                                    Example 1165                                                                  Structure                                                                      -                                                                          2  STR2395##                                                                     -                                                                          6  STR2396##                                                                     -                                                                          4  STR2397##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 257)                                                            Form: Free                                                                    Example 1166                                                                  Structure                                                                      -                                                                          2  STR2398##                                                                     -                                                                          7  STR2399##                                                                     -                                                                          6  STR2400##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 258)                                                            Form: Free                                                                    Example 1167                                                                  Structure                                                                      -                                                                          2  STR2401##                                                                     -                                                                          8  STR2402##                                                                     -                                                                          6  STR2403##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 259)                                                            Form: Free                                                                    Example 1168                                                                  Structure                                                                      -                                                                          2  STR2404##                                                                     -                                                                          9  STR2405##                                                                     -                                                                          6  STR2406##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 260)                                                            Form: Free                                                                    Example 1169                                                                  Structure                                                                      -                                                                          2  STR2407##                                                                     -                                                                          0  STR2408##                                                                     -                                                                          6  STR2409##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 261)                                                            Form: Free                                                                    Example 1170                                                                  Structure                                                                      -                                                                          2  STR2410##                                                                     -                                                                          1  STR2411##                                                                     -                                                                          6  STR2412##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 296)                                                            Form: Free                                                                    Example 1171                                                                  Structure                                                                      -                                                                          2  STR2413##                                                                     -                                                                          2  STR2414##                                                                     -                                                                          6  STR2415##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether/n-hexane                     Melting Point: 159-162° C.                                             Form: Free                                                                    Example 1172                                                                  Structure                                                                      -                                                                          2  STR2416##                                                                     -                                                                          2  STR2417##                                                                     -                                                                          3  STR2418##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/diethyl ether/n-hexane                     Melting Point: 221-224° C.                                             Form: Free                                                                    Example 1173                                                                  Structure                                                                      -                                                                          2  STR2419##                                                                     -                                                                          3  STR2420##                                                                     -                                                                          1  STR2421##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 199-202° C.                                             Form: Free                                                                    Example 1174                                                                  Structure                                                                      -                                                                          2  STR2422##                                                                     -                                                                          3  STR2423##                                                                     -                                                                          3  STR2424##                                                                     - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol/diethyl ether                              Melting Point: 215-218° C.                                             Form: Free                                                                    Example 1175                                                                  Structure                                                                      -                                                                          2  STR2425##                                                                     -                                                                          4  STR2426##                                                                     -                                                                          1  STR2427##                                                                     - Crystalline form: Colorless needles                                        Recrystallization solvent: Ethanol/diethyl ether/n-hexane                     Melting Point: 167-170° C.                                             Form: Free                                                                    Example 1176                                                                  Structure                                                                      -                                                                          2  STR2428##                                                                     -                                                                          4  STR2429##                                                                     -                                                                          3  STR2430##                                                                     - Crystalline form: White powder                                             Recrystallization solvent: Ethanol/diethyl ether/n-hexane                     Melting Point: 191-193° C.                                             Form: Free                                                                    Example 1177                                                                  Structure                                                                      -                                                                          2  STR2431##                                                                     -                                                                          5  STR2432##                                                                     -                                                                          1  STR2433##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 262)                                                            Form: Free                                                                    Example 1178                                                                  Structure                                                                      -                                                                          2  STR2434##                                                                     -                                                                          5  STR2435##                                                                     -                                                                          3  STR2436##                                                                     - Crystalline form: Light yellow amorphous                                   NMR analysis: 263)                                                            Form: Free                                                                    Example 1179                                                                  Structure                                                                      -                                                                          2  STR2437##                                                                     -                                                                          6  STR2438##                                                                     -                                                                          3  STR2439##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 297)                                                            Form: Free                                                                    Example 1180                                                                  Structure                                                                      -                                                                          2  STR2440##                                                                     -                                                                          6  STR2441##                                                                     -                                                                          1  STR2442##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 298)                                                            Form: Free                                                                    Example 1181                                                                  Structure                                                                      -                                                                          2  STR2443##                                                                     -                                                                          7  STR2444##                                                                     -                                                                          3  STR2445##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 299)                                                            Form: Free                                                                    Example 1182                                                                  Structure                                                                      -                                                                          2  STR2446##                                                                     -                                                                          7  STR2447##                                                                     -                                                                          1  STR2448##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 300)                                                            Form: Free                                                                    Example 1183                                                                  Structure                                                                      -                                                                          2  STR2449##                                                                     -                                                                          8  STR2450##                                                                     -                                                                          3  STR2451##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 307)                                                            Form: Free                                                                    Example 1184                                                                  Structure                                                                      -                                                                          2  STR2452##                                                                     -                                                                          9  STR2453##                                                                     -                                                                          1  STR2454##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 308)                                                            Form: Free                                                                    Example 1185                                                                  Structure                                                                      -                                                                          2  STR2455##                                                                     -                                                                          0  STR2456##                                                                     -                                                                          1  STR2457##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 309)                                                            Form: Free                                                                    Example 1186                                                                  Structure                                                                      -                                                                          2  STR2458##                                                                     -                                                                          0  STR2459##                                                                     -                                                                          3  STR2460##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 310)                                                            Form: Free                                                                    Example 1187                                                                  Structure                                                                      -                                                                          2  STR2461##                                                                     -                                                                          1  STR2462##                                                                     -                                                                          1  STR2463##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 311)                                                            Form: Free                                                                    Example 1188                                                                  Structure                                                                      -                                                                          2  STR2464##                                                                     -                                                                          1  STR2465##                                                                     -                                                                          1  STR2466##                                                                     - Crystalline form: Colorless amorphous                                      NMR analysis: 312                                                             Form: Free                                                                  ______________________________________                                          238)   .sup.1 H-NMR(DMSO-d.sub.6)δ; 1.4-2.1(4H, m), 2.34(3H, s),                 2.8-5.4(4H, m), 7.09(1H, d, J=8.4Hz), 7.15-7.7                        (9H, m), 7.76(1H, d, J=2.6Hz), 10.41(1H, s)                                  239) .sup.1 H-NMR(DMSO-d.sub.6)δ; 1.5-2.2(4H, m), 2.8-5.2(4H,                    m), 7.09(1H, d, J=8.4Hz), 7.2-7.7(9H, m), 7.76                        (1H, d, J=2.6Hz), 10.63(1H, s)                                               240) .sup.1 H-NMR(CDCl.sub.3)δ; 1.65-2.2(4H, m), 2.25-2.65(6H,                   m), 2.75-4.6(4H, m), 6.8-8.15(11H, m)                                241) .sup.1 H-NMR(CDCl.sub.3)δ; 1.4-2.25(4H, m), 2.25-2.55(3H,                   m), 2.7-4.8(4H, m), 6.8-8.3(11H, m)                                  242) .sup.1 H-NMR(CDCl.sub.3)δ; 1.4-2.1(4H, m), 2.35-2.6(3H,                     m), 2.8-5.2(7H, m), 6.8-8.05(11H, m)                                 243) .sup.1 H-NMR(CDCl.sub.3)δ; 1.4-2.15(4H, m), 2.4-5.2(7H,                     m), 6.8-7.85(10H, m), 7.9-8.3(1H, m)                                 244) .sup.1 H-NMR(CDCl.sub.3)δ; 1.20-2.38(11H, m), 2.98-5.10                     (3H, m), 6.45-7.04(2H, m), 7.05-7.86(8H, m),                          8.00-8.50(1H, m)                                                             245) .sup.1 H-NMR(CDCl.sub.3)δ; 1.05-2.78(14H, m), 2.78-5.18                     (2H, m), 6.36-7.03(2H, m), 7.06-7.90(8H, m),                          7.98-8.39(1H, m)                                                             246) .sup.1 H-NMR(CDCl.sub.3)δ; 1.75-2.54(2H, m), 2.60-4.03                      (4H, m), 3.37(3H, brs), 5.17(2H, s), 6.60-6.83                        (3H, m), 6.90-7.07(1H, m), 7.07-7.20(1H, m),                                  7.22-7.50(6H, m), 7.73-7.84(1H, m)                                           247) .sup.1 H-NMR(CDCl.sub.3)δ; 1.60-2.40(2H, m), 2.45(3H, s),                   2.65-3.06(2H, m), 3.06-5.28(2H, m), 3.35(3H,                          brs, 6.59-7.60(9H, m), 7.67-7.88(1H, m), 8.12                                 (1H, brs)                                                                    248) .sup.1 H-NMR(CDCl.sub.3)δ; 1.60-2.52(2H, m), 2.64-5.32                      (4H, m), 3.37(3H, brs), 6.60-7.98(10H, m), 8.50                       (1H, brs)                                                                    249) .sup.1 H-NMR(CDCl.sub.3)δ; 1.18-3.15(12H, m), 3.40-4.38                     (5H, m), 6.58-7.75(10H, m), 8.30-8.71(1H, m)                         250) .sup.1 H-NMR(CDCl.sub.3)δ; 0.26-0.71(4H, m), 1.15-3.29                      (10H, m), 3.40-4.95(5H, m), 6.60-7.85(10H, m),                        8.18-8.68(1H, m)                                                             251) .sup.1 H-NMR(CDCl.sub.3)δ; 0.25-0.72(4H, m), 1.16-2.35                      (6H, m), 2.35-3.30(4H, m), 3.43-4.98(2H, m),                          6.57-7.94(10H, m), 8.22-8.89(1H, m)                                          252) .sup.1 H-NMR(CDCl.sub.3)δ; 0.69-2.90(9H, m), 2.90-5.10                      (5H, m), 6.40-7.85(10H, m), 8.25-8.54(1H, m)                         253) .sup.1 H-NMR(CDCl.sub.3)δ; 2.17(2H, brs), 2.34(3H, s),                      2.49(3H, s), 2.87(2H, t, J=6.0Hz), 3.10-5.00                          (2H, m), 3.70(3H, s), 6.67(1H, d, J=8.0Hz),                                   6.85-6.88(2H, m), 7.09(1H, dd, J=1.5, 8.0Hz),                                 7.21-7.50(4H, m), 7.64(1H, d, J=1.9Hz), 8.11                                  (1H, m), 8.33(1H, d, J=8.8Hz)                                                254) .sup.1 H-NMR(CDCl.sub.3)δ; 1.42-5.06(13H, m), 6.51(1H, d,                   J=7.8Hz), 6.76(1H, m), 7.01-7.63(10H, m), 8.53                        (1H, m)                                                                      255) .sup.1 H-NMR(CDCl.sub.3)δ; 1.26-4.93(16H, m), 6.69-7.73                     (10H, m), 8.62-8.84(1H, m)                                           256) .sup.1 H-NMR(CDCl.sub.3)δ; 1.45-1.90(2H, m), 1.90-2.33                      (2H, m), 2.33-3.25(4H, m), 3.60-3.93(3H, m),                          4.45-5.15(2H, m), 6.40-8.25(11H, m)                                          257) .sup.1 H-NMR(CDCl.sub.3)δ; 1.49-1.97(2H, m), 1.97-3.10                      (3H, m), 3.58-3.98(3H, m), 4.60-5.26(2H, m),                          6.44-8.36(11H, m)                                                            258) .sup.1 H-NMR(CDCl.sub.3)δ; 1.82-2.13(1H, m), 2.13-2.43                      (1H, m), 2.50(3H, s), 2.57(3H, s), 3.69-4.06(3H,                      m), 3.78(3H, s), 6.45-6.80(2H, m), 6.85-7.00(1H,                              m), 7.18-7.80(9H, m)                                                         259) .sup.1 H-NMR(CDCl.sub.3)δ; 1.72-2.05(1H, m), 2.11-2.40                      (1H, m), 2.51(3H, s), 2.57(2H, s), 3.40-4.20(3H,                      m), 3.77(3H, s), 6.35-6.64(1H, m), 6.79-6.96(1H,                              m), 7.15-8.13(9H, m)                                                         260) .sup.1 H-NMR(CDCl.sub.3)δ; 1.71-2.05(1H, m), 2.07-2.32                      (1H, m), 2.33(6H, s), 2.47(3H, s), 3.50-3.80(2H,                      m), 3.76(3H, s), 3.95-4.17(1H, m), 6.40-6.70(2H,                              m), 6.90-7.03(1H, m), 7.14-7.77(8H, m), 7.90-8.14                             (1H, m)                                                                      261) .sup.1 H-NMR(CDCl.sub.3)δ; 1.76-2.70(2H, m), 2.30(6H, s),                   2.47(3H, s), 3.23-4.40(3H, m), 3.73(3H, s),                           6.30-6.65(2H, m), 6.65-8.76(9H, m)                                           262) .sup.1 H-NMR(CDCl.sub.3)δ; 1.68-2.35(2H, m), 2.36-5.11                      [13H, m, 2.45(3H, s), 2.92(6H, s)], 6.56(1H, dd,                      J=3.1, 8.7Hz), 6.87-7.06(2H, m), 6.82(1H, d,                                  J=8.7Hz), 7.11-7.68(6H, m), 7.97(1H, brs)                                    263) .sup.1 H-NMR(CDCl.sub.3)δ; 1.69-2.30(2H, m), 2.59-5.10                      [10H, m, 2.92(6H, s)], 6.56(1H, dd, J=3.1, 8.8                        Hz), 6.72-7.90(9H, m), 8.42(1H, brs)                                         264) .sup.1 H-NMR(CDCl.sub.3)δ; 1.49(1H, brs), 182-2.01(1H,                      m), 2.03-2.26(1H, m), 2.46(3H, s), 2.54(3H, s),                       3.67-3.76(1H, m), 3.86(2H, t, J=6.8Hz), 6.67                                  (1H, d, J=8.6Hz), 6.93(1H, dd, J=8.6, 2.5Hz),                                 7.13-7.43(9H, m), 8.15(1H, brs)                                              265) .sup.1 H-NMR(CDCl.sub.3)δ; 1.58(1H, brs), 1.86-2.03(1H,                     m), 2.08-2.30(1H, m), 2.56(3H, s), 3.69-3.78(1H,                      m), 3.91(2H, t, J=6.5Hz), 6.69(1H, d, J=8.7Hz),                               6.94(1H, dd, J=8.6, 2.5Hz), 7.33-7.47(6H, m),                                 7.54-7.63(2H, m), 7.67-7.77(1H, m), 8.16(1H,                                  brs)                                                                         266) .sup.1 H-NMR(CDCl.sub.3)δ; 1.50(1H, brs), 1.76-2.23(2H,                     m), 2.42(3H, s), 2.47(3H, s), 3.55-3.94(3H, m),                       6.28-7.78(10H, m), 8.91(1H, brs)                                             267) .sup.1 H-NMR(CDCl.sub.3)δ; 1.46(1H, brs), 1.82-2.28(2H,                     m), 2.50(3H, s), 3.52-4.08(3H, m), 6.34-7.75                          (10H, m), 8.61(1H, brs)                                                      268) .sup.1 H-NMR(CDCl.sub.3)δ; 1.80-2.31(2H, m), 2.32(3H, s),                   2.48(3H, s), 3.51-3.82(2H, m), 3.95-4.15(1H, m),                      6.59(1H, d, J=8.6Hz), 6.90(1H, dd, J=8.6, 2.5                                 Hz), 7.16-7.61(9H, m), 7.88(1H, brs)                                          3.52-4.08(3H, m), 6.34-7.75                                                   (10H, m), 8.61(1H, brs)                                                      269) .sup.1 H-NMR(CDCl.sub.3)δ; 1.86-2.04(1H, m), 2.13-2.31                      (1H, m), 2.33(3H, s), 3.53-3.62(1H, m), 3.76(1H,                      dt, J=12.8, 6.4Hz), 6.60(1H, d, J=8.7Hz), 6.91                                (1H, dd, J=8.7, 2.5Hz), 7.33-7.52(6H, m), 7.54-                               7.66(2H, m), 7.73-7.82(1H, m), 8.07(1H, brs)                                 270) .sup.1 H-NMR(CDCl.sub.3)δ; 1.65-2.27(2H, m), 2.28(6H, s),                   2.48(3H, s), 3.37-4.07(3H, m), 6.33-7.91(10H,                         m), 8.20(1H, brs)                                                            271) .sup.1 H-NMR(CDCl.sub.3)δ; 1.71-2.26(2H, m), 2.28(6H, s),                   3.36-4.10(3H, m), 6.35-7.95(10H, m), 8.59(1H,                         brs)                                                                         272) .sup.1 H-NMR(CDCl.sub.3)δ; 2.02-2.23(2H, m), 2.28(3H, s),                   2.47(3H, s), 2,56(3H, s), 3.73-4.07(3H, m), 4.68                      (1H, brs), 6.61(1H, d, J=8.1Hz), 6.72-6.83(1H,                                m), 7.17-7.63(11H, m), 8.03(1H, brs)                                         273) .sup.1 H-NMR(CDCl.sub.3)δ; 1.61(1H, brs), 1.87-2.25(2H,                     m), 2.29(3H, s), 2.56(3H, s), 3.67-3.78(1H, m),                       3.91(2H, t, J=6.9Hz), 6.52-6.79(2H, m), 7.09-                                 7.15(1H, m), 7.30-7.90(8H, m), 8.23(1H, brs)                                 274) .sup.1 H-NMR(CDCl.sub.3)δ; 1.58(1H, brs), 1.82-2.23(2H,                     m), 2.27(3H, s), 2.48(3H, s), 2.50(3H, s), 3.47-                      4.05(3H, m), 6.23-6.83(2H, m), 7.00-7.50(7H, m),                              7.53-7.74(1H, m), 8.28(1H, brs)                                              275) .sup.1 H-NMR(CDCl.sub.3)δ; 1.60(1H, brs), 1.82-2.35(5H,                     m), 2.49(3H, s), 3.41-4.08(3H, m), 6.30-6.80(1H,                      m), 6.98-7.68(8H, m), 7.31-7.82(1H, m), 8.77(1H,                              brs)                                                                         276) .sup.1 H-NMR(CDCl.sub.3)δ; 1.76-2.03(2H, m), 2.27(3H, s),                   2.32(6H, s), 2.47(3H, s), 3.48-3.58(1H, m), 3.66                      (1H, dt, J=12.7, 6.1Hz), 3.97-4.14(1H, m), 6.48                               (1H, d, J=8.2Hz), 6.65-6.77(1H, m), 7.14-7.59                                 (9H, m), 7.96(1H, brs)                                                       277) .sup.1 H-NMR(CDCl.sub.3)δ; 1.75-2.04(2H, m), 2.27(3H, s),                   2.33(6H, s), 3.48-3.58(1H, m), 3.67(1H, dt,                           J=12.7, 6.1Hz), 3.98-4.16(1H, m), 6.48(1H, d,                                 J=8.2Hz), 6.72(1H, dd, J=8.2, 1.9Hz), 7.16(1H,                                d, J=1.9Hz), 7.27-7.91(8H, m), 8.31(1H, brs)                                 278) .sup.1 H-NMR(CDCl.sub.3)δ; 1.72-2.05(2H, m), 2.28(9H, s),                   2.47(3H, s), 3.16-4.34(3H, m), 6.38-7.79(10H,                         m), 8.37(1H, brs)                                                            279) .sup.1 H-NMR(CDCl.sub.3)δ; 1.65-2.07(2H, m), 2.28(9H, s),                   3.26-4.38(3H, m), 6.34-8.06(10H, m), 8.53(1H,                         brs)                                                                         280) Two stereoisomers: Both colorless amorphous                               Isomer A:                                                                     [α].sub.D.sup.22 = 0° (chloroform, c=1.0)                        .sup.1 H-NMR(CDCl.sub.3)δ; 1.04(3H, d, J=6.9Hz), 1.59                   (1H, brs), 2.25-2.45(1H, m), 2.49(3H, s), 2.52                                (3H, s), 3.53-3.69(2H, m), 3.91(1H, abq, J=7.2,                               12.9Hz), 6.60(1H, d, J=8.6Hz), 6.93(1H, dd,                                   J=8.6, 2.5Hz), 7.18-7.60(9H, m), 7.76(1H, brs)                                Isomer B:                                                                     [α].sub.D.sup.22 = 0° (chloroform, c=1.0)                        .sup.1 H-NMR(CDCl.sub.3)δ; 1.06(3H, d, J=6.9Hz), 1.60                   (1H, brs), 2.21-2.43(1H, m), 2.47(3H, s), 2.52                                (3H, s), 3.51-3.66(2H, m), 3.93(1H, abq, J=7.5,                               12.9Hz), 6.60-6.68(1H, m), 6.95(1H, dt, J=7.5,                                1.8Hz), 7.03(1H, dt, J=7.4, 1.4Hz), 7.17-7.55                                 (8H, m), 7.81(1H, brs)                                                       281) Two stereoisomers: Both colorless amorphous                               Isomer A:                                                                     [α].sub.D.sup.22 = 0° (chloroform, c=1.0)                        .sup.1 H-NMR(CDCl.sub.3)δ; 1.04(3H, d, J=6.9Hz), 1.55                   (1H, brs), 2.23-2.46(1H, m), 2.53(3H, s), 3.53-                               3.67(2H, m), 3.91(1H, abq, J=7.1, 12.9Hz), 6.61                               (1H, d, J=8.6Hz), 6.93(1H, dd, J=8.6, 2.5Hz),                                 7.28-7.52(6H, m), 7.54-7.65(2H, m), 7.70-7.79                                 (1H, m), 8.16(1H, brs)                                                        Isomer B:                                                                     [α].sub.D.sup.22 = 0° (chloroform, c=1.0)                        .sup.1 H-NMR(CDCl.sub.3)δ; 1.06(3H, d, J=6.9Hz), 1.61                   (1H, brs), 2.21-2.42(1H, m), 2.51(3H, s), 3.48-                               3.67(2H, m), 3.90(1H, abq, J=7.4, 12.9Hz), 6.59-                              6.67(1H, m), 6.94(1H, dt, J=7.5, 1.9Hz), 7.03                                 (1H, dt, J=7.4, 1.4Hz), 7.23-7.75(8H, m), 8.41                                (1H, brs)                                                                    282) Two stereoisomers: Both colorless amorphous                               Isomer A:                                                                     [α].sub.D.sup.22 = 0° (chloroform, c=1.0)                        .sup.1 H-NMR(CDCl.sub.3)δ; 0.99(3H, d, J=6.5Hz), 1.37                   (1H, brs), 2.61-2.40(1H, m), 2.46(3H, s), 2.48                                (3H, s), 3.38-3.96(3H, m), 6.30-7.28(10H, m),                                 8.26(1H, brs)                                                                 Isomer B:                                                                     [α].sub.D.sup.22 = 0° (chloroform, c=1.0)                        .sup.1 H-NMR(CDCl.sub.3)δ; 1.03(3H, d, J=6.7Hz), 1.44(1H,                       brs), 2.17-2.40(1H, m), 2.45(3H, s), 2.47(3H,                         s), 3.40-3.98(3H, m), 6.47-7.73(10H, m), 8.23                                 (1H, brs)                                                                    283) Two stereoisomers: Both colorless amorphous                               Isomer A:                                                                     [α].sub.D.sup.22 = 0° (chloroform, c=1.0)                        .sup.1 H-NMR(CDCl.sub.3)δ; 1.00(3H, d, J=6.6Hz), 1.40                   (1H, brs), 2.18-2.42(1H, m), 2.47(3H, s), 3.36-                               4.02(3H, m), 6.32-7.78(10H, m), 8.55(1H, brs)                                 Isomer B:                                                                     [α].sub.D.sup.22 = 0° (chloroform, c=1.0)                        .sup.1 H-NMR(CDCl.sub.3)δ; 1.03(3H, d, J=6.5Hz), 1.39                   (1H, brs), 2.14-2.39(1H, m), 2.45(3H, s). 3.34-                               3.98(3H, m), 6.53-7.98(10H, m), 8.78(1H, brs)                                284) .sup.1 H-NMR(CDCl.sub.3)δ; 1.05-1.25(3H, m), 1.25-2.80                      (10H, m), 3.00-5.10(3H, m), 6.75-8.40(11H, m)                        285) .sup.1 H-NMR(CDCl.sub.3)δ; 1.00-2.80(12H, m), 3.00-5.10                     (3H, m), 6.70-7.80(10H, m), 8.03-8.80(1H, m)                         286) .sup.1 H-NMR(CDCl.sub.3)δ; 0.95-2.80(15H, m), 2.80-5.15                     (3H, m), 6.70-7.05(2H, m), 7.10-7.80(10H, m),                         7.95-8.45(1H, m)                                                             287) .sup.1 H-NMR(CDCl.sub.3)δ; 0.80-2.60(16H, m), 2.60-5.05                     (4H, m), 6.70-7.70(10H, m), 7.85-8.40(1H, m)                         288) .sup.1 H-NMR(CDCl.sub.3)δ; 1.30-2.60(8H, m), 2.60-5.10                      (3H, m), 6.60-7.95(10H, m), 8.25-8.70(1H, m)                         289) .sup.1 H-NMR(CDCl.sub.3)δ; 1.27-4.91(19H, m), 6.68-7.73                     (10H, m), 8.40-8.71(1H, m)                                           290) .sup.1 H-NMR(CDCl.sub.3)δ; 1.81-2.54(6H, m), 2.15(3H, s),                   2.41(3H, s), 2.46(3H, s), 3.61-3.71(3H, m),                           6.91-7.43(10H, m), 8.06(1H, s)                                               291) .sup.1 H-NMR(CDCl.sub.3)δ; 1.86-2.50(3H, m), 2.28(9H, s),                   2.49(3H, s), 6.60-7.47(10H, m), 7.75(1H, m)                          292) .sup.1 H-NMR(CDCl.sub.3)δ; 1.15-2.55(13H, m), 2.55-5.10                     (3H, m) 6.60-8.40(11H, m)                                            293) .sup.1 H-NMR(CDCl.sub.3)δ; 1.15-2.45(10H, m), 2.55-5.10                     (3H, m), 6.60-7.80(10H, m), 8.30-8.70(1H, m)                         294) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10-2.60(4H, m), 2.41(6H, s),                   2.49(3H, s), 3.76(3H, s), 2.60-5.20(3H, m),                           6.50-6.80(3H, m), 6.90-7.60(6H, m), 8.13(1H, s),                              8.30(1H, d, J=8.5Hz)                                                         295) .sup.1 H-NMR(CDCl.sub.3)δ; 1.15-2.50(4H, m), 2.41(6H, s),                   2.60-5.20(3H, m), 3.77(3H, s), 6.50-7.50(8H, m),                      7.65-7.80(1H, m), 8.31(1H, d, J=8.4Hz), 8.61                                  (1H, s)                                                                      296) .sup.1 H-NMR(CDCl.sub.3)δ; 1.55-3.13(12H, m), 2.44(3H,                      s), 4.60-5.14(2H, m), 6.28(1H, dd, J=2.5, 8.5                         Hz), 6.48(1H, d, J=8.5Hz), 6.99(1H, d, J=2.5                                  Hz), 7.07-7.58(8H, m), 7.80(1H, brs)                                         297) .sup.1 H-NMR(CDCl.sub.3)δ; 1.01-2.88, 3.22-4.41, 4.90-5.28                  [total 18H, 1.17(3H, t, J=7.2Hz), 2.40(3H, s),                        3.77(3H, s)], 6.55(1H, d, J=8.1Hz), 6.60-7.98                                 (8H, m), 8.23-8.75(2H, m)                                                    298) .sup.1 H-NMR(CDCl.sub.3)δ; 1.00-3.04, 3.24-4.45. 4.91-5.27                  [total 21H, m, 1.17(3H, t, J=7.0Hz), 2.39(3H,                         s), 2.50(3H, s), 3.75(3H, s)], 8.56(1H, d, J=8.3                              Hz), 6.69(1H, d, J=8.3Hz), 6.82-7.75(7H, m),                                  8.05-8.49(2H, m)                                                             299) .sup.1 H-NMR(CDCl.sub.3)δ; 1.21-4.62, 4.90-5.43(total 15H,                  m), 5.70-6.11(1H, m), 6.35-7.90(9H, m), 8.07-8.92                     (2H, m)                                                                      300) .sup.1 H-NMR(CDCl.sub.3)δ; 1.20-4.68, 5.01-5.3[total 18H,                   m, 2.50(3H, s)], 5.72-6.14(1H, m), 6.49-7.69(9H,                      m), 8.01-8.58(2H, m)                                                         301) .sup.1 H-NMR(CDCl.sub.3)δ; 1.25-2.80(14H, m), 3.00-5.10                     (6H, m), 6.40-8.00(11H, m)                                           302) .sup.1 H-NMR(CDCl.sub.3)δ; 1.30-2.90(11H, m), 3.00-5.10                     (6H, m), 6.40-7.80(10H, m), 8.00-8.35(1H, m)                         303) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10-2.80(16H, m), 2.85-5.15                     (6H, m), 6.40-7.80(11H, m)                                           304) .sup.1 H-NMR(CDCl.sub.3)δ; 1.10-2.80(13H, m), 2.90-5.10                     (6H, m), 6.40-7.85(10H, m), 7.90-8.20(1H, m)                         305) .sup.1 H-NMR(CDCl.sub.3)δ; 1.27-5.28(19H, m), 3.75(3H,                      s), 6.51(1H, d, J=7.9Hz), 6.69-6.81(2H, m),                           7.05-7.49(6H, m), 8.14(1H, m), 8.27(1H, d, J=8.4                              Hz)                                                                          306) Two stereoisomers: Both colorless amorphous                               Isomer A:                                                                     [α].sub.D.sup.22 = 0° (chloroform, c=1.0)                        .sup.1 H-NMR(CDCl.sub.3)δ; 0.78-1.02(3H, m), 2.23-2.52                  (1H, m) 2.39(6H, s), 2.48(3H, s), 3.17-4.30(3H,                               m), 6.85-7.84(10H, m), 8.17(1H, brs)                                          Isomer B:                                                                     [α].sub.D.sup.22 = 0° (chloroform, c=1.0)                        .sup.1 H-NMR(CDCl.sub.3)δ; 0.73-1.00(3H, m), 2.17-2.52                  (1H, m) 2.39(6H, s), 2.49(3H, s), 3.15-4.33(3H,                               m), 6.36-7.55(8H, m), 7.58-7.83(2H, m), 8.19(1H,                              brs)                                                                         307) .sup.1 H-NMR(CDCl.sub.3)δ; 1.25-4.44, 4.98-5.41 [total 17H,                 m, 2.40(3H, s), 3.76(3H, s)], 5.72-6.13(1H, m),                       6.56(1H, d, J=8.4Hz), 6.69(1H, d, J=7.9Hz),                                   6.77-7.93(7H, m), 8.32(1H, d, J=8.3Hz), 8.49-                                 8.95(1H, m)                                                                  308) .sup.1 H-NMR(CDCl.sub.3)δ; 1.23-5.42(20H, m), 5.78-6.09                     (1H, m), 6.56(1H, d, J=8.3Hz), 6.61-7.82(8H, m),                      8.14(1H, s), 8.30(1H, d, J=8Hz)                                              309) .sup.1 H-NMR(CDCl.sub.3)δ; 1.20-2.70(11H, m), 2.80-4.90                     (9H, m), 6.40-7.70(10H, m), 8.30-8.70(1H, m)                         310) .sup.1 H-NMR(CDCl.sub.3)δ; 1.20-2.80(8H, m), 2.85-5.05                      (9H, m), 6.40-7.80(10H, m), 8.10-8.50(1H, m)                         311) .sup.1 H-NMR(CDCl.sub.3)δ; 1.20-2.75(13H, m), 2.80-5.10                     (9H, m), 6.40-8.00(11H, m)                                           312) .sup.1 H-NMR(CDCl.sub.3)δ; 1.20-2.80(10H, m), 2.90-5.10                     (9H, m), 6.40-7.80(10H, m), 8.00-8.40(1H, m)                       ______________________________________                                    

EXAMPLE 1189

By using di-p-toluoyl-L-tartaric acid monohydride ordi-p-toluoyl-D-tartaric acid monohydride, the compound obtained in aboveExample 408 is optically resolved to give the following compounds.

(+)-5-Dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride White amorphous

[α]_(D) ²⁵ =+234° (methanol, c=0.2)

Purity; more than 99% ee, determined by HPLC using an optical acitivecolumn

HPLC conditions;

Mobile phase; n-hexane:ethanol:diethylamine=950:50:1

Flow rate; 1.0 ml/min.

Column; CHIRALCEL OD, 25 cm×0.46 cm (manufactured by Daicel ChemicalInd. Ltd.)

Concentration of sample; 0.1% in methanol

Retention time; 34 minutes

¹ H-NMR (DMSO-d₆) δ; 0.85-1.20, 1.56-4.06, 4.94-5.21 (total 13H, m),2.36 (3H, s), 6.79 (1H, d, J=7.6 Hz), 7.12-7.60 (8H, m), 7.62 (2H, d,J=8.4 Hz), 8.00 (1H, d, J=7.6 Hz), 10.43 (1H, s), 11.80 (1H, brs)

(-)-5-Dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride White amorphous

[α]_(D) ²⁵ =-23.1° (methanol, c=0.2)

Purity; more than 99% ee, determined by HPLC using an optical activecolumn, and the conditions are the same as above except that theretention time is 40 minutes.

¹ H-NMR (DMSO-d₆) δ; 0.83-1.19, 1.55-4.06, 4.94-5.20 (total 13H, m),2.36 (3H, s), 6.80 (1H, d, J=7.8 Hz), 7.12-7.60 (8H, m), 7.63 (2H, d,J=8.5 Hz), 8.00 (1H, d, J=7.8 Hz), 10.44 (1H, s), 11.74 (1H, brs)

Pharmacological Test

Experiment 1: V₁ receptor binding assay

Using rat liver plasma membrane preparations prepared according toIchihara's method [cf: Akira Ichihara, J. Bio. Chem., 258, 9283 (1983)],the plasma membrane (50000 dpm, 2×10⁻¹⁰ M) of [³ H]-Arg-vasopressin anda test compound (60 μg, 10⁻⁸ -10⁻⁴ M) are incubated at 37° C. for 10minutes in 100 mM Tris-HCl buffer (pH: 8.0, 250 μl) containing 5 mMMgCl₂, 1 mM EDTA and 0.1% BSA. After incubation, the mixture is filteredthree times using the glass filter (GF/F) so as to separate the membranepreparation combined with vasopressin and then washed with the buffer (5ml). This glass filter is taken out and mixed with liquid scintillationcocktail. The amount of [³ H]-vasopressin combined with the membrane ismeasured by liquid scintillation counter and the rate of the inhibitoryeffect of the test compound is estimated according to the followingequation. ##EQU1## C¹ : The amount of [³ H]-vasopressin combined withthe membrane in the presence of the test compound (in prescribedamount).

C⁰ : The amount of [³ H]-vasopressin combined with the membrane in theabsence of the test compound.

B¹ : The amount of [³ H]-vasopressin combined with the membrane in thepresence of the excess amount of vasopressin (10⁻⁶ M).

The results are expressed as IC₅₀ values, which is the concentration ofthe test compound required to achieve the inhibitory effect in the rateof 50%.

The results are shown in the following Table 10.

Test compound

1. 1-(4-Benzoylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

2. 1-[4-(3-Chlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

3. 1-[4-(3-Methoxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

4. 1-[4-(3-Cyanobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

5. 1-[4-(3-Aminobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

6. 1-[4-(2,3-Dimethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

7. 1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

8.1-[4-(2-Trifluoromethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

9. 1-[4-(2-Nitrobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

10. 1-[4-(3,5-Dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

11. 1-[4-(3,3-Dimethylbutyrylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

12. 1-[4-(2-Cyclohexylacetylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

13. 1-[4-(2-Phenylacetylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

14. 1-(4-Cyclohexylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

15. 1-(4-Cycloheptylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

16. 1-(4-Cyclooctylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

17.1-(4-Tricyclo[3.3.1.1]decanylcarbonylamino-benzoyl)-1,2,3,4-tetrahydroquinoline

18. 1-[4-(α-Naphthylcarbonylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

19. 1-[4-(3-Thenoyl)benzoyl]-1,2,3,4-tetrahydroquinoline

20. 1-[2-(β-Naphthylcarbonylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

21. 1-[4-(4-Methoxyanilinocarbonyl)benzoyl]-1,2,3,4-tetrahydroquinoline

22. 1-[4-(2-Methylanilinocarbonyl)benzoyl]-1,2,3,4-tetrahydroquinoline

23. 1-[4-(3-Chloroanilinocarbonyl)benzoyl]-1,2,3,4-tetrahydroquinoline

24.1-[4-(3,5-Dichloroanilinocarbonyl)benzoyl]-1,2,3,4-tetrahydroquinoline

25. 1-(4-Cyclohexylaminocarbonylbenzoyl)-1,2,3,4-tetrahydroquinoline

26.1-(4-Cyclohexylcarbonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

27. 1-(4-Benzoylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

28.1-[4-(2-Methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

29.1-[4-(3-Methoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

30.1-[4-(3-Chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

31. 1-[4-(3-Cyanobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

32.1-[4-(3,5-Dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

33.1-[4-(2,3-Dimethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

34.1-(4-Cyclohexylcarbonylaminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine

35. 1-(4-Benzoylaminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine

36. 1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,4,5,6-hexahydrobenzazocine

37.1-[4-(3-Methoxybenzoylamino)benzoyl]-1,2,3,4,5,6-hexahydrobenzazocine

38.1-[4-(2,3-Dimethylbenzoylamino)benzoyl]-1,2,3,4,5,6-hexahydrobenzazocine

39.1-[4-(3,5-Dichlorobenzoylamino)benzoyl]-1,2,3,4,5,6-hexahydrobenzazocine

40.1-(4-Cyclohexylcarbonylaminobenzoyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine

41.1-[4-(3-Methylbenzoylamino)benzoyl]-1,2,3,5-tetrahydro-4,1-benzoxazepine

42.1-[4-(2,3-Dimethylbenzoylamino)benzoyl]-1,2,3,5-tetrahydro-4,1-benzoxazepine

43.1-[4-(3,5-Dichlorobenzoylamino)benzoyl]-1,2,3,5-tetrahydro-4,1-benzoxazepine

44.3-Methyl-1-(4-cyclohexylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

45. 3-Methyl-1-(4-benzoylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

46.3-Methyl-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

47.3-Methyl-1-[4-(3-methoxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

48.3-Methyl-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

49.3-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

50.4-Methyl-1-(4-cyclohexylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoxalin

51.4-Methyl-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoxaline

52.4-Methyl-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoxaline

53.4-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoxaline

54. 2-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

55.4-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

56. 1-[4-(2-Bromobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

57. 1-[4-(3-Nitrobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

58.1-[4-(3-Trifluoromethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

59.1-[4-(3-Ethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

60.1-[4-(3,5-Dimethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

61.1-[4-(2-Chloro-4-nitrobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

62.1-[4-(2,4-Dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

63.1-[4-(2-Chloro-6-fluorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

64.1-[4-(2,6-Dimethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

65.1-[4-(2-Chloro-4-aminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

66.1-[4-(2-Chloro-4-acetylaminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

67. 1-[4-(3-Aminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

68.1-{4-[2-(4-Isopropylaminobutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride

69.1-[4-(3-Hydroxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

70.1-{4-[2-(4-Aminobutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

71.1-{4-[2-(2-Diethylaminoethoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride

72.1-{4-[2-(4-Acetylaminobutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

73.1-{4-[2-(6-Phthalimidohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

74.1-{4-[2-(6-Morpholinohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

75.1-{4-[2-(6-[4-Methyl-1-piperazinyl]hexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepinedihydrochloride

76.1-(3-Methoxy-4-cyclohexylcarbonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

77.1-(3-methoxy-4-benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

78.1-[3-Methyl-4-(2-methylbenzoylamino)benzoy]-2,3,4,5-tetrahydro-1H-benzazepine

79.4-Methyl-1-(4-cyclohexylcarbonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinehydrochloride

80.4-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-l,4-benzodiazepinehydrochloride

81.4-Methyl-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinehydrochloride

82.4-Methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinehydrochloride

83.4-Methyl-1-[4-(3-methoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

84.4-Methyl-1-[4-(3-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

85.4-Methyl-1-[4-(2,3,5-trichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

86.4-Propyl-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinehydrochloride

87.5-Methyl-1-(4-benzoylaminobenzoyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

88.5-Methyl-1-(4-cyclohexylcarbonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

89.5-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

90.5-Methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

91.5-Methyl-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

92.4-Methyl-1-[3-methoxy-4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

93.3-(1-Pyrrolidinyl)-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

94.6-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

95.6-Methoxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

96.3-Hydroxymethyl-1-(4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

97.4-Methylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

98.3-Amino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

99.3-Acetylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

100.4-Dimethylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

101.1-[4-(2-t-Butylaminoacetylamino)benzoyl]-2,3,4,5-tetrahydroquinoline-1H-benzazepine

102.1-{4-[2-(N-Cyclohexyl-N-ethyl)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

103.1-{4-[2-(1-Piperidinyl)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

104.1-[4-(2-Phenoxyacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

105.1-[4-(2-Phthalimidoacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

106.1-{4-[2-(1,1-Dimethyl-2-phenoxyethyl)aminoacetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

107.1-{4-[2-(3-Methylphenoxy)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

108.1-{4-[2-(3-Methoxyanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

109.1-{4-[2-(β-Naphthyloxy)acetyamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

110.1-{4-[2-(4-Methylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

111.1-{4-(2-(3-Methoxyphenoxy)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

112.1-[4-(4-Pyridylcarbonylaminobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

113.1-{4-[2-(2,4-Dimethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

114.1-{4-[2-(N-Ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

115.1-{4-[2-(N-Allylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

116.1-{4-[2-(2-Chloroanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

117.1-{4-[2-(4-Acetyloxybutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

118.1-[4-(2-Carboxymethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

119.1-[4-(2-Carbamoylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

120.1-{4-[2-(4-Hydroxybutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

121.1-[4-(2-Ethoxycarbonylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

122.6-Fluoro-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

123.6-Fluoro-1-{4-[di-(3,5-dichlorobenzoyl)amino]benzoyl}-1,2,3,4-tetrahydroquinoline

124.1-[4-(2-Diethylaminocarbonylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

125.1-{4-[2-(2-[(N-(2-hydroxyethyl)-N-methylamino]ethoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzoazepinehydrochloride

126.1-[4-(2-Methylanilinocarbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

127.1-[4-(2-Chlorophenylsulfonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

128.1-{4-[2-(4-Aminomethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

129.1-{4-[2-(N-Phenyl-N-(3-acetylaminopropyl)amino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

130.1-{4-[2-(N-Phenyl-N-propargylamino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

131.4-(N-Methyl-N-ethylamino)-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

132.5-Dimethylamino-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

133.4-Dimethylamino-1-[3-methoxy-4-(2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

134.5-Dimethylamino-1-[3-methoxy-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

135.1-[4-(2,3-Dimethylbenzoylamino)benzoyl]-4-ethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

136.1-[4-(3,5-Dichlorobenzoylamino)benzoyl]-4-isopropyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

137.1-[4-(2-Methylbenzoylamino)benzoyl]-5-methyl-1,2,3,4,5,6-hexahydro-1,5-benzodiazocine

138.1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydro-5,1-benzoxazepine

139.5-Oxo-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

140.4-Methyl-1-[2-chloro-4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

141.5-Methylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

142.5-(N-Acetyl-N-methylamino)-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

143.5-Hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

144.4-Dimethylamino-1-[3-methoxy-4-(2,3-dimethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

145.4-Dimethylaminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

146.4-Dimethylaminomethyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

147.5-Methoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

148.4-Methyl-1-[3-methyl-4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

149.5-Methoxy-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

150.4-Dimethylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

151.4-Acetyloxy-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

152.5-Hydroxyimino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

153.5-Acetyloxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

154.5-Ethoxycarbonylmethoxy-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

155.4-Allylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

156.5-Dimethylamino-1-[3-methoxy-4-(2,3,5-trichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

157.4-[4-(2-Methylbenzoylamino)benzoyl]-3,4-dihydro-2H-1,4-benzothiazine

158.5-Dimethylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

159.5-Dimethylamino-1-[4-(2-methylanilinocarbonyl)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

160.5-Ethoxycarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

161.5-(4-dimethylaminobutoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

162.5-Carboxymethoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

163.5-Dimethylaminocarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

164.5-Carbamoylmethoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

165.5-Dimethylamino-1-[3-ethoxy-4-(2-methyl-benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

166.5-[4-(2-Methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1,5-benzothiazepine

167.5-Amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

168.5-Dimethylamino-1-[3-hydroxy-4-[2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

169.5-n-Propylamino-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

170.5-Dimethylamino-1-[3-benzyloxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

171.5-[4-(2-Methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1,5-benzothiazepin-1-oxide

172.5-[3-(Phthalimid-1-yl)-propoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

173.5-(3-Aminopropoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

174.5-(3-Acetylaminopropoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

175.5-Dimethylamino-1-[2-chloro-4-(2-t-butylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

176.5-Methylamino-1-[2-chloro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

177.5-Dimethylamino-1-[2-methoxy-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

178.5-Hydroxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

179.5-Dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

180.5-Dimethylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

181.5-Methylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

182.5-Methylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

183.5-Dimethylamino-1-[2-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

184.5-Dimethylamino-1-[2-chloro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

185.5-Methylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl-2,3,4,5-tetrahydro-1H-benzazepine

186.5-Cyclopropylamino-1-[2-chloro-4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

187.5-Dimethylaminocarbonyloxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

188.5-Dimethylamino-1-[4-(2-trifluoromethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

189.5-Dimethylamino-1-[3-(2-chlorobenzoyloxy)-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

190.5-(N-Methyl-N-Allylamino)-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

191.5-Carbamoyloxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

192.1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,5-tetrahydro-4,1-benzothiazepine

193.4-Oxo-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

194.1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,5-tetrahydro-4,1-benzothiazepine-1,1-dioxide

195.5-Methylaminocarbonylmethoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

196.5-Methylaminocarbonyloxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahyro-1H-benzazepine

197.5-Dimethylamino-1-[2-dimethylamino-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

198.5-Methylamino-1-[2-chloro-4-(2-trifluoromethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

199.5-Cycloropropylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

200.5-Cyclopropylamino-1-[2-chloro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

201.5-Allylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

202.5-(1-Piperidinyl)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

203.5-(4-Benzyl-1-piperazinyl)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

204.5-(1-Pyrrolidinyl)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

205.5-(4-Acetyl-1-pipetazinyl)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

206.5-(4-Methyl-1-piperazinyl)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

207. 1-[4-(2-Chlorobenzoylamino)benzoyl]-2,3-dihydro-1H-benzazepine

208.5-Methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

209.5-Methylidene-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

210.5-Hydroxy-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

211.5-(1-Morpholino)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

212.5-Dimethylamino-1-[4-(2-fluorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

213.5-Dimethylamino-1-[4-(2,4-difluorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

214.4-Hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

215.5-Hydroxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

216.5-Dimethylamino-4-hydroxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

217. 1-[4-(2-Methylbenzoylamino)benzoyl]-1,2-dihydroquinoline

218.5-Dimethylamino-1-12-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(the compound of Example 979)

219.5-Dimethylamino-1-[2-methyl-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

220.5-Dimethylamino-1-[2-methyl-4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

221.5-Methylamino-1-{2-chloro-4-(2-(N-ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

222.5-Hydroxy-1-{2-chloro-4-[2-(N-ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

223.5-Dimethylamino-1-[2-fluoro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

224.5-Methylamino-4-hydroxy-1-[2-chloro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride

225.5-Hydroxymethyl-5-hydroxy-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

226.5-Dimethylamino-1-[2-fluoro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

227.5-Dimethylamino-1-[3-methyl-4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

228.5-(N-Methyl-N-ethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

229.5-Ethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

230.5-Dimethylamino-1-[4-(3,5-difluorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

231.5-Acetyloxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

232.5-Dimethylamino-1-[3-fluoro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

233.4,4-Dimethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

234.5-Acetyloxyimino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

235.5-Methylsulfonyloxymethyl-1-[4-(2-methyl-benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

236.5,5-Epoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

237.5-Hydroxymethyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

238.5-Hydroxy-1-[2-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

239.5-Dimethylamino-1-[4-(2-carbamoylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

240.5-Hydroxy-6-methyl-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

241.5-(2-Dimethylaminoethyl)amino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

242.5-Hydroxymethyl-5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

243.5-Methylaminomethyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

244.5-Aminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

245.5-[N-Methyl-N-(3-methoxy-2-hydroxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

246.5-[N-Methyl-N-(3-diethylamino-2-hydroxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

247.5-Dimethylamino-1-[3-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

248.5-Dimethylamino-1-(3-methoxy-4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

249.5-Dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine.hydrochloride

250.5-Azidomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

251.7-[4-(2-Chlorobenzoylamino)benzoyl]-1-methyl-1,2,3,4a,5,6,7,11b-octahydro-3-oxo[1]benzazepino[4,5-b]-[1,4]oxazine

252.5-Benzylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

253.5-Amino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

254.5-Dimethylamino-4-methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

255.5-Acetylaminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

256.5-Hydroxy-4-methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

257.5-[2-(2-Pyridyl)ethylamino]-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

258.5-(N-Methyl-N-methanesulfonylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

259.5-(N-Methyl-N-benozylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

260.5-Ethoxycarbonylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

261.5-Methyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

262.5-(N-Methyl-N-ethoxycarbonylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

263.5-Cyclopentylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

264.5-[N-Methyl-N-(2,3-dihydroxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

265.5-(N-Methyl-N-cyanomethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

266.5-(N-Methyl-N-carbamoylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

267.5-{N-Methyl-N-[3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propyl]amino}-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

268.5-Dimethylaminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

269.5-Formylaminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

270.5-[N-Methyl-N-(3-acetyloxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

271.5-[N-Methyl-N-(3-hydroxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

272. Potassium{1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin-5-yl}imino-o-sulfonate

273.5-Dimethylamino-1-(4-benzoylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

274.5-(1-Benzyl-4-piperidinyl)amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

275.5-(2-Dimethylaminoacetyloxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

276.5-Dimethylamino-1-[4-(3-methoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

277.5-((4-Methyl-1-piperazinyl)carbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

278.5-Morpholinocarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

279.5-Thiomorpholinocarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

280.5-Anilinocarbonylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

281.5-(1-Oxothiomorpholino)carbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

282.5-Hydrazino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

283.5-Methylaminocarbonylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

284.5-[(2-a-Carbamoyl-1-pyrrolidinyl)carbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

285.-5-(Carbamoylmethylaminocarbonylmethoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

286.5-(1,1-Dioxothiomorpholino)carbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

287.7-Chloro-5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

288.5-[(4-Acetyl-1-piperazinyl)carbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

289.5-Dimethylamino-1-[4-(3-nitrobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

290.5-[(4-Pyridyl)methylaminocarbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

291.5-[2-(Methylamino)acetylamino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

292.5-Dimethylamino-1-[4-(3-aminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

293.5-{[N-Methyl-N-(2-hydroxyethyl)amino]carbonylmethoxy}-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

294.5-Dimethylamino-1-[3-(2-diethylaminoethoxy)-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

295.5-[N-Methyl-N-(dimethylaminocarbonylmethyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

296. Potassium2-[N-methyl-N-{1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin-5-yl}amine]acetate

297.5-(N-Methyl-N-[2-(1-imidazolyl)acetyl]amino}-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

298.5-Dimethylamino-1-[4-(2-dimethylaminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

299.5-[(2-Aminoacetyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

300.5-Dimethylamino-1-[4-(3-acetylaminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

301.5-(2-t-Butoxycarbonylaminoacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

302.5-Methylamino-7-chloro-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

303.5-Dimethylamino-7-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

304.5-Dimethylamino-7-chloro-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

305.5-Dimethylamino-1-[4-(phenylacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

306.5-Dimethylamino-1-[4-(3-phenylpropionylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

307.5-Methylamino-7-chloro-1-{4-[(N-ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

308.5-Dimethylamino-7-chloro-1-{4-[(N-ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

309.5-Dimethylamino-1-[4-(2-bromobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

310.5-Cyclopropylamino-7-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

311.5-Cyclopropylamino-7-chloro-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

312.5-hydroxy-1-{4-[2-(4-isopropylaminobutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

313.5-Dimethylaminocarbonylmethoxy-1-{4-[(N-ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

314.5-(N-Methyl-N-ethylamino)-1-[2-chloro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

315.5-Dimethylamino-1-{4-[(2-chloroanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

316.5-Dimethylamino-1-{4-[(2-methylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

317.5-Dimethylamino-1-{4-[(N-methyl-2-methylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

318.5-Methylamino-9-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

319.5-Dimethylamino-1-[4-(phenoxyacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

320.6-Methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4,5,6-hexahydrobenzazocine

321.5-Methylamino-7-chloro-1-[3-methoxy-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

322.5-Cyclopropylamino-7-chloro-1-[3-methoxy-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

323.5-Methylamino-7-chloro-1-[3-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

                  TABLE 10                                                        ______________________________________                                        Test                   Test                                                     Comp. IC.sub.50 Comp. IC.sub.50                                               No. (μM) No. (μM)                                                     ______________________________________                                        26       0.071         78      0.10                                             27 0.095 88 0.34                                                              28 0.056 90 0.38                                                              29 0.15 114 0.011                                                             30 0.15 115 0.012                                                             32 0.30 116 0.04                                                              33 0.092 117 0.22                                                             36 0.41 119 0.049                                                             46 0.40 120 0.29                                                              56 0.025 121 0.45                                                             57 0.46 124 0.15                                                              58 0.40 125 0.091                                                             59 0.31 130 0.023                                                             60 0.18 143 0.15                                                              62 0.098 147 0.28                                                             63 0.14 161 0.14                                                              64 0.069 163 0.22                                                             67 0.34 164 0.15                                                              68 0.013 172 0.26                                                             69 0.066 173 0.15                                                             70 0.041 174 0.14                                                             71 0.18 187 0.45                                                              72 0.12 188 0.47                                                              74 0.10 192 0.054                                                             75 0.069 193 0.17                                                             76 0.042 195 0.17                                                             77 0.085 196 0.40                                                             207 0.16 284 0.29                                                             208 0.11 285 0.18                                                             209 0.074 286 0.40                                                            214 0.27 287 0.064                                                            215 0.13 288 0.26                                                             222 0.096 290 0.21                                                            231 0.16 293 0.19                                                             235 0.088 298 0.29                                                            236 0.16 302 0.071                                                            238 0.39 303 0.19                                                             244 0.23 304 0.21                                                             250 0.19 307 0.024                                                            252 0.36 308 0.11                                                             255 0.046 309 0.43                                                            256 0.049 310 0.065                                                           266 0.29 311 0.078                                                            269 0.48 312 0.056                                                            274 0.11 313 0.032                                                            275 0.18 315 0.38                                                             277 0.23 316 0.47                                                             278 0.30 321 0.059                                                            279 0.15 322 0.044                                                            280 0.47 323 0.064                                                            281 0.18                                                                    ______________________________________                                    

Pharmacological Test

Experiment 2: V₂ receptor binding assay

Using rat kidney plasma membrane preparations prepared according to 0.Hechter's method [cf: J. Bio. Chem., 253, 3211 (1978)], the plasmamembrane (100000 dpm, 4×10⁻¹⁰ M) of [³ H]-Arg-vasopressin and a testcompound (0.6 mg, 10⁻¹⁰ -10⁻⁵ M) are incubated at 4° C. for 3 hours in100 mM Tris-HCl buffer (pH: 8.0, 250 μl) containing 5 mM MgCl₂, 1 mMEDTA and 0.1% BSA. After incubation, the mixture is filtered using theglass filter (GF/F) so as to separate the membrane preparation combinedwith vasopressin and then washed twice with the buffer (5 ml). Thisglass filter is taken out and mixed with liquid scintillation cocktail.The amount of [³ H]-vasopressin combined with the membrane is measuredby liquid scintillation counter and the rate of the inhibitory effect ofthe test compound is estimated according to the following equation.##EQU2## C¹ : The amount of [³ H]-vasopressin combined with the membranein the presence of the test compound (in prescribed amount).

C⁰ : The amount of [³ H]-vasopressin combined with the membrane in theabsence of the test compound.

B¹ : The amount of [³ H]-vasopressin combined with the membrane in thepresence of the excess amount of vasopressin (10⁻⁶ M).

The results are expressed as IC₅₀ values, which is the concentration ofthe test compound required to achieve the inhibitory effect in the rateof 50%.

The results are shown in the following Table 11.

                  TABLE 11                                                        ______________________________________                                        Test                   Test                                                     Comp. IC.sub.50 Comp. IC.sub.50                                               No. (μM) No. (μM)                                                     ______________________________________                                        1        0.98          28      0.018                                            2 0.20 29 0.069                                                               3 0.40 30 0.029                                                               4 0.58 31 0.098                                                               5 1.2 32 0.016                                                                6 0.076 33 0.007                                                              7 0.20 34 0.049                                                               8 0.32 35 0.20                                                                9 0.53 36 0.028                                                               10 0.082 37 0.16                                                              11 1.05 38 0.029                                                              12 1.97 39 0.071                                                              13 1.02 40 0.33                                                               14 0.23 41 0.20                                                               15 0.13 42 0.063                                                              16 0.17 43 0.17                                                               17 0.23 44 0.050                                                              18 1.0 45 0.19                                                                19 1.7 46 0.018                                                               20 1.4 47 0.20                                                                21 1 48 0.021                                                                 22 0.33 49 0.063                                                              23 1.07 50 1.3                                                                24 1.09 51 0.40                                                               25 1.67 52 0.32                                                               26 0.025 53 1.6                                                               27 0.070 54 0.11                                                              55 0.091 86 0.58                                                              56 0.037 87 0.046                                                             57 0.16 88 0.021                                                              58 0.14 89 0.035                                                              59 0.24 90 0.014                                                              60 0.15 91 0.005                                                              61 0.090 92 0.41                                                              62 0.023 93 0.52                                                              63 0.046 94 0.095                                                             64 0.007 95 0.089                                                             65 0.081 96 0.039                                                             66 0.45 97 0.024                                                              67 0.050 98 0.45                                                              68 0.19 99 1.6                                                                69 0.12 100 0.011                                                             70 0.012 101 0.60                                                             71 0.085 102 0.29                                                             72 0.16 103 0.54                                                              74 0.51 104 0.37                                                              75 0.30 105 0.72                                                              76 0.017 106 0.44                                                             77 0.090 107 0.032                                                            78 0.084 108 0.12                                                             79 0.53 109 0.49                                                              80 0.070 110 0.044                                                            81 0.15 111 0.087                                                             82 0.17 112 0.29                                                              83 0.73 113 0.28                                                              84 0.11 114 0.006                                                             85 0.068 115 0.006                                                            116 0.039 146 0.056                                                           117 0.24 147 0.009                                                            118 0.55 148 0.34                                                             119 0.059 149 0.004                                                           120 0.28 150 0.14                                                             121 0.18 151 0.18                                                             122 0.10 152 0.039                                                            123 0.10 153 0.063                                                            124 0.13 154 0.063                                                            125 0.28 155 0.028                                                            126 0.062 156 0.15                                                            127 0.99 157 0.38                                                             128 0.23 158 0.018                                                            129 0.29 159 0.020                                                            130 0.007 160 0.020                                                           131 0.027 161 0.009                                                           132 0.013 162 0.059                                                           133 0.022 163 0.009                                                           134 0.048 164 0.010                                                           135 0.081 165 0.098                                                           136 0.18 166 0.070                                                            137 0.41 167 0.032                                                            138 0.11 168 0.083                                                            139 0.10 169 0.071                                                            140 0.024 170 0.25                                                            141 0.010 171 0.87                                                            142 0.008 172 0.023                                                           143 0.008 173 0.008                                                           144 0.02 174 0.007                                                            145 0.06 175 0.038                                                            176 0.004 206 0.088                                                           177 0.15 207 0.045                                                            178 0.012 208 0.007                                                           179 0.040 209 0.004                                                           180 0.034 210 0.004                                                           181 0.038 211 0.12                                                            182 0.005 212 0.035                                                           183 0.26 213 0.033                                                            184 0.023 214 0.058                                                           185 0.005 215 0.006                                                           186 0.030 216 0.91                                                            187 0.029 217 0.37                                                            188 0.039 218 0.022                                                           189 0.087 219 0.023                                                           190 0.082 220 0.026                                                           191 0.009 221 0.024                                                           192 0.011 222 0.010                                                           193 0.036 223 0.022                                                           194 0.21 224 0.38                                                             195 0.010 225 0.030                                                           196 0.013 226 0.019                                                           197 0.99 227 0.029                                                            198 0.040 228 0.029                                                           199 0.019 229 0.029                                                           200 0.024 230 0.020                                                           201 0.023 231 0.007                                                           202 0.14 232 0.020                                                            203 0.070 233 0.15                                                            204 0.11 234 0.14                                                             205 0.074 235 0.006                                                           236 0.006 267 0.12                                                            237 0.041 268 0.018                                                           238 0.020 269 0.003                                                           239 0.17 270 0.046                                                            240 0.022 271 0.030                                                           241 0.006 272 0.40                                                            242 0.17 273 0.027                                                            243 0.40 274 0.024                                                            244 0.018 275 0.018                                                           245 0.059 276 0.032                                                           246 0.027 277 0.016                                                           247 0.048 278 0.013                                                           248 0.060 279 0.008                                                           250 0.12 280 0.045                                                            251 0.094 281 0.011                                                           252 0.063 282 0.38                                                            253 0.052 283 0.096                                                           254 0.016 284 0.019                                                           255 0.005 285 0.008                                                           256 0.004 286 0.019                                                           257 0.045 287 0.007                                                           258 0.20 288 0.015                                                            259 0.25 289 0.071                                                            260 0.13 290 0.021                                                            261 0.011 291 0.13                                                            262 0.029 292 0.18                                                            263 0.053 293 0.065                                                           264 0.030 294 0.33                                                            265 0.025 295 0.026                                                           266 0.013 296 0.25                                                            297 0.051 311 0.013                                                           298 0.10 312 0.29                                                             299 0.22 313 0.012                                                            300 0.48 314 0.096                                                            301 0.14 315 0.025                                                            302 0.011 316 0.060                                                           303 0.025 317 0.072                                                           304 0.024 318 0.060                                                           305 0.038 319 0.058                                                           306 0.077 320 0.039                                                           307 0.010 321 0.012                                                           308 0.023 322 0.025                                                           309 0.015 323 0.014                                                           310 0.008                                                                   ______________________________________                                    

Experiment 3: Anti-antidiuretic activity (effect on endogenous ADH)

A test compound or solvent (dimethylformamide) is administered into acaudal vein of untreated, unrestrained SD rats (male, weight: 300-350 g)and the amount of urine, which is spontaneously excreted for a period of2 hours thereafter, is collected and measured by using a metabolicgauge. During this measurement, the rats are allowed to take water andfeed freely.

The amount of urine of control rats (solvent-treated group) is regardedas 100%, and the results are expressed as ED₃ value, which is the doseof the test compound to be required to excrete the urine by three timesthan that of the control rats. The results are shown in the followingTable 12.

                  TABLE 12                                                        ______________________________________                                        Test compound No.                                                                             ED.sub.3 (mg/kg)                                              ______________________________________                                        6               10                                                              33 1.9                                                                        178 4.2                                                                       249 0.4 .sup.*)                                                             ______________________________________                                         .sup.*) Physicological saline solution was used as a solvent instead of       dimethylformamide.                                                       

Using the suitable starting materials, the compounds of the followingTable 13 are obtained in the same manner as in Examples 1 and 382.

                  TABLE 13                                                        ______________________________________                                        1 #STR2467##                                                                  ______________________________________                                        Example 1190                                                                    Structure                                                                      -                                                                                                     2  R.sup.2 : 2-OCH.sub.3                              -                                                                                                     3  STR2469##                                          - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 210-213° C.                                             Form: Free                                                                    Example 1191                                                                  Structure                                                                      -                                                                                                     4  R.sup.2 : 2-CH.sub.3                               -                                                                                                     5  STR2471##                                          - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 184.5-186° C.                                           Form: Free                                                                    Example 1192                                                                  Structure                                                                      -                                                                                                     6  R.sup.2 : H                                        -                                                                                                     7  STR2473##                                          - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 201.5-202.5° C.                                         Form: Free                                                                    Example 1193                                                                  Structure                                                                      -                                                                                                     8  R.sup.2 : 2-Cl                                     -                                                                                                     9  STR2475##                                          - Crystalline form: White powder                                             Recrystallization solvent: Dichloromethane/diethyl ether                      Melting Point: 159-162° C. (decomposed)                                Form: Free                                                                    Example 1194                                                                  Structure                                                                      -                                                                                                     0  R.sup.2 : 2-OCH.sub.3                              -                                                                                                     1  STR2477##                                          - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 237-240° C.                                             Form: Free                                                                    Example 1195                                                                  Structure                                                                      -                                                                                                     2  R.sup.2 : 2-OCH.sub.3                              -                                                                                                     3  STR2479##                                          - Crystalline form: White powder                                             Recrystallization solvent: Diethyl ether/dichloromethane                      Melting Point: 269-272.5° C.                                           Form: Free                                                                    Example 1196                                                                  Structure                                                                      -                                                                                                     8  R.sup.2 : H                                        -                                                                                                     1  STR2481##                                          - Crystalline form: Colorless prisms                                         Recrystallization solvent: Ethanol/dichloromethane                            Melting Point: 201-202° C.                                             Form: Free                                                                    Example 1197                                                                  Structure                                                                      -                                                                                                     4  R.sup.2 : 2-CH.sub.3                               -                                                                                                     5  STR2483##                                          - Crystalline form: White powder                                             Recrystallization solvent: Methanol                                           Melting Point: 204-206° C.                                             Form: Free                                                                    Example 1198                                                                  Structure                                                                      -                                                                                                     6  R.sup.2 : 2-Cl                                     -                                                                                                     7  STR2485##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 313)                                                            Form: Free                                                                    Example 1199                                                                  Structure                                                                      -                                                                                                     8  R.sup.2 : 2-CH.sub.3                               -                                                                                                     9  STR2487##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 314)                                                            Form: Free                                                                    Example 1200                                                                  Structure                                                                      -                                                                                                     0  R.sup.2 : 2-CH.sub.3                               -                                                                                                     1  STR2489##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 315)                                                            Form: Free                                                                    Example 1201                                                                  Structure                                                                      -                                                                                                     2  R.sup.2 : 2-OCH.sub.3                              -                                                                                                     3  STR2491##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 316)                                                            Form: Free                                                                    Example 1202                                                                  Structure                                                                      -                                                                                                     4  R.sup.2 : 2-Cl                                     -                                                                                                     5  STR2493##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 317)                                                            Form: Free                                                                    Example 1203                                                                  Structure                                                                      -                                                                                                     6  R.sup.2 : 2-OCH.sub.3                              -                                                                                                     7  STR2495##                                          - Crystalline form: Light brown amorphous                                    NMR analysis: 318)                                                            Form: Hydrochloride                                                           Example 1204                                                                  Structure                                                                      -                                                                                                     8  R.sup.2 : 2-OCH.sub.3                              -                                                                                                     9  STR2497##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 319)                                                            Form: Free                                                                    Example 1205                                                                  Structure                                                                      -                                                                                                     0  R.sup.2 : 2-CH.sub.3                               -                                                                                                     1  STR2499##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 320)                                                            Form: Hydrochloride                                                           Example 1206                                                                  Structure                                                                      -                                                                                                     2  R.sup.2 : 2-CH.sub.3                               -                                                                                                     3  STR2501##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 321)                                                            Form: Hydrochloride                                                           Example 1207                                                                  Structure                                                                      -                                                                                                     4  R.sup.2 : 2-OCH.sub.3                              -                                                                                                     5  STR2503##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 322)                                                            Form: Free                                                                    Example 1208                                                                  Structure                                                                      -                                                                                                     6  R.sup.2 : 2-OCH.sub.3                              -                                                                                                     7  STR2505##                                          - Crystalline form: Light yellow prisms                                      Recrystallization solvent: Ethyl acetate/n-hexane                             Melting Point: 187-189° C.                                             Form: Free                                                                    Example 1209                                                                  Structure                                                                      -                                                                                                     8  R.sup.2 : H                                        -                                                                                                     9  STR2507##                                          - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 227-231° C.                                             Form: Free                                                                    Example 1210                                                                  Structure                                                                      -                                                                                                     0  R.sup.2 : 2-CH.sub.3                               -                                                                                                     1  STR2509##                                          - Crystalline form: White powder                                             Recrystallization solvent: Methanol/diethyl ether                             Melting Point: 191-192° C.                                             Form: Free                                                                    Example 1211                                                                  Structure                                                                      -                                                                                                     2  R.sup.2 : 2-CH.sub.3                               -                                                                                                     3  STR2511##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 323)                                                            Form: Free                                                                    Example 1212                                                                  Structure                                                                      -                                                                                                     4  R.sup.2 : 2-CH.sub.3                               -                                                                                                     5  STR2513##                                          - Crystalline form: Colorless amorphous                                      NMR analysis: 324)                                                            Form: Free                                                                    Example 1213                                                                  Structure                                                                      -                                                                                                     6  R.sup.2 : 2-CH.sub.3                               -                                                                                                     7  STR2515##                                          - Crystalline form: White amorphous                                          NMR analysis: 325)                                                            Form: Hydrochloride                                                         ______________________________________                                         313) .sup.1 HNMR (CDCl.sub.3) δ; 1.40-2.30(4H, m), 2.36(3H, s),         2.60-2.92(2H, m), 4.35-5.18(2H, m), 6.69-6.87(1H, m), 6.87-7.04(1H, m),       7.05-8.06(8H, m), 8.25-8.60(1H, m)                                            314) .sup.1 HNMR (CDCl.sub.3) δ; 1.43-2.26(4H, m), 2.38(3H, s),         2.42(3H, s), 2.61-2.91(1H, m), 2.91-3.40(1H, m), 4.49-5.08(2H, m),            6.40-7.68(10H, m), 7.68-7.93(1H, m)                                           315) .sup.1 HNMR (CDCl.sub.3) δ; 1.32-2.25(4H, m), 2.25-2.54(3H, m)     2.59-3.42(2H, m), 4.45-5.08(2H, m), 6.40-7.80(10H, m), 8.00-8.38(1H, m)       316) .sup.1 HNMR (CDCl.sub.3) δ; 1.42-1.89(2H, m), 1.90-2.30(2H, m)     2.57-2.95(2H, m), 3.36-3.64(3H, m), 4.51-5.17(2H, m), 6.52-7.80(10H, m),      8.11-8.41(1H, m)                                                              317) .sup.1 HNMR (CDCl.sub.3) δ; 1.18-2.25(4H, m), 2.25-2.59(3H, m)     2.59-2.88(1H, m), 2.88-4.32(1H, m), 4.32-5.05(2H, m), 6.44-8.08(10H, m),      8.52-9.00(1H, m)                                                              318) .sup.1 HNMR (DMSOd.sub.6) δ; 1.35-2.45(7H, m), 2.6-3.0(8H, m),     3.2-4.2(6H, m), 4.45-4.85(2H, m), 6.75-7.7(11H, m)                            319) .sup.1 HNMR (CDCl.sub.3) δ; 1.20-2.89, 3.22-4.33, 4.48-5.05,       5.75-6.32 [total 17H, m {2.45 (s)}], 6.52-7.78(10H, m), 8.10-8.71(1H, m)      320) .sup.1 HNMR (DMSOd.sub.6) δ; 1.49-3.05[11H, m{2.35(s),             2.40(s)}], 3.71-5.04(3H, m), 5.28-5.88(1H, m), 6.64-7.98(10H, m), 8.58(3H     brs), 10.32, 10.48(total 1H, each s)                                          321) .sup.1 HNMR (DMSOd.sub.6) δ; 1.50-3.70[17H, m{2.36, 2.40(each      s), 2.87, 2.89, 2.94(each s)}], 4.05-5.08(3H, m), 5.90-6.28(1H, m),           6.62-7.98(10H, m), 10.36, 10.52(total 1H, each brs), 10.94(1H, brs)           322) .sup.1 HNMR (CDCl.sub.3) δ; 1.53-2.91[14H, m{2.42, 2.47(each       s)}], 3.09-4.27(5H, m), 4.70-5.12(1H, m), 5.89-6.36(1H, m), 6.57-7.94(11H     m)                                                                            323) .sup.1 HNMR (CDCl.sub.3) δ; 1.32-2.23(2H, m), 2.23-2.68(7H, m)     2.68-3.84(8H, m), 3.84-5.23(4H, m), 6.47-7.88(11H, m)                         324) .sup.1 HNMR (CDCl.sub.3) δ; 1.45-2.32(5H, m), 2.44(3H, s),         2.63-3.21(1H, m), 3.40-5.01(4H, m), 6.28-7.93(10H, m), 8.10-8.43(1H, m)       325) .sup.1 HNMR (DMSOd.sub.6) δ; 0.71-3.46, 4.15-4.44[total 23H,       2.35(s), 2.42(s), 2.86(s)], 6.71-7.88(10H, m), 10.16-10.58(2H, m)        

What is claimed is:
 1. A method for antagonizing vasopressin whichcomprises administering to a subject a therapeutically effective amountof a benzoheterocyclic compound of the formula: ##STR2516## wherein R¹is a hydrogen atom, a halogen atom, a C₁ -C₆ alkyl, an amino havingoptionally a C₁ -C₆ alkyl substituent, or a C₁ -C₆ alkoxy;R² is ahydrogen atom, a halogen atom, a C₁ -C₆ alkoxy, a phenyl-(C₁ -C₆)alkoxy, hydroxy, a C₁ -C₆ alkyl, an amino having optionally a C₁ -C₆alkyl substituent, a carbamoyl-substituted C₁ -C₆ alkoxy, anamino-substituted C₁ -C₆ alkoxy having optionally a C₁ -C₆ alkylsubstituent, or a benzoyloxy which has optionally a halogen substituenton the phenyl ring; R³ is a group of the formula: ##STR2517## or a groupof the formula: ##STR2518## R⁴ is a hydrogen atom, a benzoyl which hasoptionally a halogen substituent on the phenyl ring or a C₁ -C₆ alkyl;R⁵ is a group of the formula: ##STR2519## wherein R¹⁶ is a halogen atom,a C₁ -C₆ alkyl which has optionally a substituent selected from ahalogen atom and hydroxy, hydroxy, a C₁ -C₆ alkoxy, a C₁ -C₆alkanoyloxy, a C₁ -C₆ alkylthio, a C₁ -C₆ alkanoyl, carboxy, a C₁ -C₆alkoxycarbonyl, a cyano; a nitro, an amino which has optionally asubstituent selected from a C₁ -C₆ alkyl and a C₁ -C₆ alkanoyl, aphenyl, a C₃ -C₈ cycloalkyl, a C₂ -C₆ alkanoyloxy-substituted C₁ -C₆alkoxy, a carboxy-substituted C₁ -C₆ alkoxy, a halogen-substituted C₁-C₆ alkoxy, a carbamoyl-substituted C₁ -C₆ alkoxy, a hydroxy-substitutedC₁ -C₆ alkoxy, a C₁ -C₆ alkoxycarbonyl-substituted C₁ -C₆ alkoxy, aphthalimido-substituted C₁ -C₆ alkoxy; an aminocarbonyl-(C₁ -C₆) alkoxyhaving a C₁ -C₆ alkyl substituent; or a group of the formula:##STR2520## wherein A is a C₁ -C₆ alkylene, and R⁶ and R⁷ are the sameor different and are each a hydrogen atom, a C₁ -C₆ alkyl havingoptionally a hydroxy substituent, a C₁ -C₆ alkanoyl or benzoyl, or R⁶and R⁷ may bind together with the nitrogen atom to which they are bondedto form a 5- or 6-membered saturated heterocyclic group with or withoutan intervening nitrogen or oxygen atom wherein the heterocyclic group isone member selected from the group consisting of pyrrolidinyl,piperidinyl, piperazinyl and morpholino, and has optionally asubstituent selected from piperidinyl and a C₁ -C₆ alkyl; and m is aninteger of 0 to 3, or R⁵ is a phenyl-(C₁ -C₆) alkoxycarbonyl, a C₁ -C₆alkanoyl, a phenyl-(C₂ -C₆) alkanoyl, a C₃ -C₈ cycloalkyl-(C₂ -C₆)alkanoyl, a C₃ -C₈ cycloalkylcarbonyl, tricyclo(3.3.1.1)decanylcarbonyl,naphthylcarbonyl, pyridylcarbonyl, fulroyl, thenoyl, a phenoxy-(C₂ -C₆)alkanoyl which phenyl ring has optionally 1 to 3 substituents selectedfrom a C₁ -C₆ alkyl, a C₁ -C₆ alkoxy and an amino having optionally a C₁-C₆ alkanoyl substituent, a phthalimido-substituted C₂ -C₆ alkanoyl, aC₁ -C₆ alkoxycarbonyl-(C₂ -C₆) alkanoyl, a carboxy-(C₂ -C₆) alkanoyl, anaphthyloxy-(C₂ -C₆) alkanoyl, a halogen-substituted C₁ -C₆ alkanoyl, agroup of the formula: ##STR2521## wherein R⁸ is a hydrogen atom, a C₁-C₆ alkyl, a phenyl-(C₁ -C₆) alkoxycarbonyl, a carbamoyl-(C₁ -C₆) alkyl,an amino-(C₂ -C₆) alkanoyl having optionally a C₁ -C₆ alkyl substituent,or a C₁ -C₆ alkanoyl, an anilinocarbonyl which has optionally a C₁ -C₆alkyl substituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonylwhich has optionally a substituent selected from a halogen atom and a C₁-C₆ alkyl on the phenyl ring, quinolylsulfonyl, or a group of theformula: ##STR2522## wherein B is a C₁ -C₆ alkylene, n is an integer of0 or 1, and R⁹ and R¹⁰ are the same or different and are each a hydrogenatom, a C₁ -C₆ alkyl having optionally a hydroxy substituent, a C₃ -C₈cycloalkyl, a phenyl-(C₁ -C₆) alkyl, a C₁ -C₆ alkanoyl, a C₂ -C₆alkenyl, a phenoxy-(C₁ -C₆) alkyl, a phenyl which has optionally 1 to 3substituents selected from an amino-(C₁ -C₆) alkyl having optionally aC₁ -C₆ alkanoyl substituent, a C₁ -C₆ alkyl, a C₁ -C₆ alkoxy and ahalogen atom, a phthalimido-substituted C₁ -C₆ alkyl, an amino-(C₁ -C₆)alkyl having optionally a C₁ -C₆ alkanoyl substituent, a C₂ -C₆ alkynyl,or an amino-(C₁ -C₆) alkyl having optionally a C₁ -C₆ alkyl substituent,or R⁹ and R¹⁰ may bind together with the nitrogen atom to which they arebonded to form a 5- or 6-membered saturated heterocyclic group with orwithout being intervened with a nitrogen or an oxygen atom wherein theheterocyclic group is one member selected from the group consisting ofpyrrolidinyl, piperidinyl, piperazinyl and morpholino, and hasoptionally a substituent selected from a C₁ -C₆ alkyl, a C₁ -C₆alkoxycarbonyl and piperidinyl,R¹¹ is a hydrogen atom or a C₁ -C₆ alkyl,R¹² is a C₃ -C₈ cycloalkyl, or a phenyl which has optionally 1 to 3substituents selected from a C₁ -C₆ alkoxy, a C₁ -C₆ alkyl and a halogenatom, W is a group of the formula: --(CH₂)_(p) -- wherein p is aninteger of 3 to 5, or a group of the formula: --CH═CH--(CH₂)_(q) --wherein q is an integer of 1 to 3, wherein one of the CH₂ groupsassociated with the formula CH₂ associated with the --(CH₂)_(p) -- andthe --CH═CH--(CH₂)_(q) -- is replaced by a group of the formula:##STR2523## wherein R¹³ is a hydrogen atom, a C₃ -C₈ cycloalkyl, or a C₁-C₆ alkyl, and further said --(CH₂)_(p) -- group and said--CH═CH--(CH₂)_(q) -- group having optionally 1 to 3 substituentsselected from a C₁ -C₆ alkyl having optionally a hydroxy substituent, aC₁ -C₆ alkoxycarbonyl, carboxy, hydroxy, oxo, a C₁ -C₆ alkanoyloxyhaving optionally a halogen substituent, an amino-(C₁ -C₆) alkyl havingoptionally a substituent selected from a C₁ -C₆ alkyl and a C₁ -C₆alkanoyl, a C₁ -C₆ alkanoyloxy-substituted C₁ -C₆ alkyl, a C₁ -C₆alkylsulfonyloxy-(C₁ -C₆) alkyl, an azido-(C₁ -C₆) alkyl, a group of theformula: ##STR2524## an aminocarbonyloxy having optionally a C₁ -C₆alkyl substituent, a C₁ -C₆ alkoxy, a C₁ -C₆ alkoxycarbonyl-substitutedC₁ -C₆ alkoxy, a carboxy-substituted C₁ -C₆ alkoxy, an aminocarbonyl-(C₁-C₆) alkoxy having optionally a C₁ -C₆ alkyl substituent, an amino-(C₁-C₆) alkoxy having optionally a substituent selected from a C₁ -C₆ alkyland a C₁ -C₆ alkanoyl, a phthalimido-substituted C₁ -C₆ alkoxy,hydroxy-imino, a C₁ -C₆ alkanoyloxy-imino, a C₁ -C₆ alkylidene, ahalogen atom, azido, sulfoxyimino, a group of the formula: ##STR2525##wherein R⁸¹ is a hydrogen atom or a C₁ -C₆ alkyl, provided that said##STR2526## binds to said --(CH₂)_(p) -- or said --CH═CH--(CH₂)_(q) --to form a 6-membered ring, a group of the formula: ##STR2527## wherein Ais as defined above in this claim, and R⁸² and R⁸³ are the same ordifferent and are each a hydrogen atom, a C₁ -C₆ alkyl, acarbamoyl-substituted C₁ -C₆ alkyl, a hydroxy-substituted C₁ -C₆ alkyl,or a pyridyl-(C₁ -C₆) alkyl, or R⁸² and R⁸³ may bind together with thenitrogen atom to which they are bonded to form a 5- or 6-memberedsaturated heterocyclic group with or without being intervened with anitrogen, oxygen or sulfur atom wherein the heterocyclic group is onemember selected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl, morpholino, and thiomorpholino, and has optionally asubstituent selected from oxo, a C₁ -C₆ alkyl, a C₁ -C₆ alkanoyl, andcarbamoyl, and a group of the formula: ##STR2528## wherein n is asdefined above in this claim, and R¹⁴ and R¹⁵ are the same or differentand are each a hydrogen atom, a C₁ -C₆ alkyl, a C₂ -C₆ alkenyl, a C₁ -C₆alkanoyl, a C₃ -C₈ cycloalkyl, an oxiranyl-substituted C₁ -C₆ alkyl, aC₁ -C₆ alkyl having 1 to 2 substituents selected from a C₁ -C₆ alkoxy,hydroxy and an amino having optionally a C₁ -C₆ alkyl substituent, aphenyl-(C₁ -C₆) alkyl, a pyridyl-(C₁ -C₆) alkyl, a C₁ -C₆ alkylsulfonyl,benzoyl, a C₁ -C₆ alkoxycarbonyl, anilinocarbonyl, an aminocarbonylhaving optionally a C₁ -C₆ alkyl substituent, a cyano-substituted C₁ -C₆alkyl, a C₁ -C₆ alkoxycarbonyl-substituted C₁ -C₆ alkyl, acarbamoyl-substituted C₁ -C₆ alkyl, a carboxy-substituted C₁ -C₆ alkyl,a tetrahydropyranyloxy-substituted C₁ -C₆ alkyl, a C₁ -C₆alkanoyloxy-substituted C₁ -C₆ alkyl, a piperidinyl having optionally aphenyl-(C₁ -C₆) alkyl substituent on the piperidine ring, a halogensubstituted C₁ -C₆ alkanoyl, an imidazolyl-substituted C₂ -C₆ alkanoyl,an amino-(C₂ -C₆) alkanoyl having optionally a substituent selected froma C₁ -C₆ alkyl and a C₁ -C₆ alkoxycarbonyl, an aminocarbonyl-(C₁ -C₆)alkyl having optionally a C₁ -C₆ alkyl substituent, or a phenyl-(C₁ -C₆)alkoxycarbonyl, or R¹⁴ or R¹⁵ may bind together with the nitrogen atomto which they are bonded to form a 5- or 6-membered saturatedheterocyclic group with or without being intervened with a nitrogen oroxygen atom, wherein the heterocyclic group is one member selected fromthe group consisting of pyrrolidinyl, piperidinyl, piperazinyl, andmorpholino, and may optionally have a substituent selected from a C₁ -C₆alkyl, a phenyl-(C₁ -C₆) alkyl or a C₁ -C₆ alkanoyl, and apharmaceutically acceptable salt thereof.
 2. The method according toclaim 1, wherein W is a group of the formula: --(CH₂)_(p) -- wherein pis an integer of 3 to 5, and one of the CH₂ groups is replaced by agroup of the formula: ##STR2529## wherein R¹³ is a hydrogen atom, a C₃-C₈ cycloalkyl, or a C₁ -C₆ alkyl.
 3. The method according to claim 1,wherein W is a group of the formula: --CH═CH--(CH₂)_(q) -- wherein q isan integer of 1-3 and one of the CH₂ groups is replaced by a group ofthe formula: ##STR2530## wherein R¹³ is a hydrogen atom, a C₃ -C₈cycloalkyl, or a C₁ -C₆ alkyl.
 4. The method according to claim 2,wherein p in the group of the formula: --(CH₂)_(p) -- is
 3. 5. Themethod according to claim 2, wherein p in the group of the formula:--(CH₂)_(p) -- is
 4. 6. The method according to claim 2, wherein p inthe group of the formula: --(CH₂)_(p) -- is
 5. 7. The method accordingto claim 5, wherein the heterocyclic group of the formula: ##STR2531##is 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine.
 8. The method according toclaim 1, wherein the benzoheterocyclic compound is1-[4-(2-mehtylbenzoylamino)benzoyl]-4-methyl-2,3,4,5-tetrahydro-1H-benzodiazepine.9. The method according to claim 1, wherein the heterocyclic group ofthe formula: ##STR2532## is 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine.